Skip to main content

Advertisement

SpringerLink
Log in

Alterations in Neuropeptides in Aging and Disease

Pathophysiology and Potential for Clinical Intervention

  • Physiological Aspects of Aging
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Summary

Marked specific and selective changes in the levels of some neuropeptides in age-related diseases, such as senile dementia of the Alzheimer (SDAT) or Lewy body (SDLT) types, Parkinson’s disease, Huntington’s disease and major depressive disorder, versus normal aging have been noted. However, the levels of most neuropeptides are normal.

The only 2 peptides consistently altered in SDAT are somatostatin and corticotrophin-releasing hormone both of which are reduced. In Huntington’s disease, the level of substance P in the basal ganglia is reduced suggesting a preferential vulnerability of spiny neurones in this disease. In Parkinson’s disease, substance P is attenuated in the basal ganglia while somatostatin is reduced in the neocortex. These and other results suggest that substance P deficits are related to movement disorders while somatostatin deficits are related to cognitive impairment. SDLT is a type of dementia with features common to both SDAT and Parkinson’s disease, although the changes in neuropeptides suggest that neurochemically the disease is more closely related to SDAT.

In major depressive disorder, the level of corticotrophin-releasing hormone is reduced while there is a reciprocal increase in corticotrophin-releasing hormone receptors suggesting that the neurones remain functional.

Potential clinical intervention has been limited by problems such as poor penetration of agents into the brain and the short half-lives of neuropeptide agonists and antagonists. However, some currently available agents may act, at least in part, through modulation of neuropeptide pathways, e.g. carbamazepine and alprazolam both modulate the corticotrophin-releasing hormone system in animals, and both have clinically proven antidepressant activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Agren H, Lundqvist G. Low levels of somatostatin in human CSF mark depressive episodes. Psychoneuroendocrinology 9: 233–248, 1985

    Article  Google Scholar 

  • Alho H, Costa E, Ferrero P, Fujimoto M, Cosenzu-Murphy D, et al. Diazepam-binding inhibitor: a neuropeptide located in selected neuronal populations of rat brain. Science 229: 179–182, 1985

    Article  PubMed  CAS  Google Scholar 

  • Allen JM, Cross AJ, Crow TJ, Javoy-Agid F, Agid Y, et al. Dissociation of neuropeptide Y and somatostatin in Parkinson’s disease. Brain Research 337: 197–200, 1985

    Article  PubMed  CAS  Google Scholar 

  • Allen JM, Ferrier IN, Roberts GW, Cross AJ, Adrian TE, et al. Elevation of neuropeptide Y in substantia innominata of Alzheimer’s type dementia. Journal of the Neurological Sciences 64: 325–331, 1984

    Article  PubMed  CAS  Google Scholar 

  • Alzheimer A. Uber eine eigenartige Erkrankung der Hirnrinde. Allemmeine Z Psychiatrie Psychisch-Gerichtliche Med 64: 146–148, 1907

    Google Scholar 

  • Arai H, Moroji I, Kosaka K. Somatostatin and vasoactive intestinal polypeptide in post-mortem brains from patients with Alzheimer-type dementia. Neuroscience Letters 52: 73–78, 1984

    Article  PubMed  CAS  Google Scholar 

  • Arai H, Takahashi T, Kimura M, Noguchi I, Minami M, et al. Postmortem human brain tissue investigations of neurotransmitters in aging and in AD/SDAT. Biological Psychiatry 29: 295, 1991

    Google Scholar 

  • Aronin N, Cooper PE, Lorenz LJ, Bird ED, Sugar SM, et al. Somatostatin is increased in the basal ganglia in Huntington’s disease. Annals of Neurology 13: 519–526, 1983

    Article  PubMed  CAS  Google Scholar 

  • Aronin N, DiFiglia M, Graveland GA, Schwartz WJ, Wu JY. Localization of immunoreactive enkephalins in GABA synthesizing neurons of the rat neostriatum. Brain Research 300: 376–380, 1984

    Article  PubMed  CAS  Google Scholar 

  • Ball JA, Burnet PWJ, Bretherton-Watt D, Bloom SR. Increase in diazepam binding inhibitor-like immunoreactivity (51-70) in Huntington’s disease. Journal of the Neurological Sciences 88: 171–184, 1988

    Article  Google Scholar 

  • Banki CM, Bissette G, Arato M, Nemeroff CB. Elevation of immunoreactive CSF TRH in depressed patients. American Journal of Psychiatry 145: 1526–1531, 1988

    PubMed  CAS  Google Scholar 

  • Banki CM, Bissette G, Arato M, O’Connor L, Nemeroff CB. CSF corticotropin-releasing factor-like immunoreactivity in depression and schizophrenia. American Journal of Psychiatry 144: 873–877, 1987

    PubMed  CAS  Google Scholar 

  • Banki CM, Karmacsi L, Bissette G, Nemeroff CB. Cerebrospinal fluid neuropeptides in dementia. Biological Psychiatry 32: 452–456, 1992

    Article  PubMed  CAS  Google Scholar 

  • Barbaccia ML, Costa E, Ferrero P, Guidotti A, Roy A, et al. Diazepam-binding inhibitor. Brain neuropeptide present in human spinal fluid: studies in depression, schizophrenia and Alzheimer’s disease. Archives of General Psychiatry 43: 1143–1147, 1986

    Article  PubMed  CAS  Google Scholar 

  • Baronti F, Conant KE, Giuffra M, Davis TL, Brughitta G, et al. Opioid peptides in Parkinson’s: effects of dopamine repletion. Brain Research 560: 92–96, 1991

    Article  PubMed  CAS  Google Scholar 

  • Beach TG, McGeer EG. Neocortical substance P neurons in the baboon: an immunohistochemical finding. Neuroscience Letters 41: 265–270, 1983

    Article  PubMed  CAS  Google Scholar 

  • Beal MF, Benoit R, Bird ED, Martin JB. Immunoreactive somatostatin-281 12 is increased in Huntington’s disease. Neuroscience Letters 56: 377–380, 1985a

    Article  PubMed  CAS  Google Scholar 

  • Beal MF, Clevens RA, Chattha GK, MacGarvey UM, Mazurek MF, et al. Galanin-like immunoreactivity is unchanged in Alzheimer’s disease and Parkinson’s dementia cerebral cortex. Journal of Neurochemistry 51: 1935–1941, 1988a

    Article  PubMed  CAS  Google Scholar 

  • Beal MF, Ellison DW, Mazurek MF, Swartz KJ, Malloy JR, et al. A detailed examination of substance P in pathologically graded cases of Huntington’s disease. Journal of the Neurological Sciences 84: 51–61, 1988b

    Article  PubMed  CAS  Google Scholar 

  • Beal MF, Growdon JH, Mazurek MF, Martin JB. CSF somatostatin-like immunoreactivity in dementia. Neurology 36: 294–297, 1986a

    Article  PubMed  CAS  Google Scholar 

  • Beal MF, Martin JB. Neuropeptides in neurological disease. Annals of Neurology 20: 547–565, 1986

    Article  PubMed  CAS  Google Scholar 

  • Beal MF, Mazurek MF, Chattha GK, Bird ED, Martin JB. Neuropeptide Y immunoreactivity is reduced in Alzheimer’s disease cerebral cortex. Annals of Neurology 20: 282–288, 1986b

    Article  PubMed  CAS  Google Scholar 

  • Beal MF, Mazurek MF, Lorenz LJ. Substance P-like immunoreactivity is reduced in Alzheimer’s disease cerebral cortex. Neurology 37: 1205–1209, 1987

    Article  PubMed  CAS  Google Scholar 

  • Beal MF, Mazurek MF, Martin JB. Somatostatin immunoreactivity is reduced in Parkinson’s disease dementia with Alzheimer’s changes. Brain Research 397: 386–388, 1986c

    Article  PubMed  CAS  Google Scholar 

  • Beal MF, Mazurek MF, Tran VT, Chatta G, Bird ED, et al. Reduced numbers of somatostatin receptors in cerebral cortex in Alzheimer’s disease. Science 229: 289–291, 1985b

    Article  PubMed  CAS  Google Scholar 

  • Beckwith BE, Till RE, Scheider V. Vasopressin analogue (DDAVP) improves memory in human males. Peptides 5: 819–822, 1984

    Article  PubMed  CAS  Google Scholar 

  • Berrettini WH, Nurnberger JI, Gold PW, Chretien M, Chrousos GP, et al. Neuropeptides in human. Life Sciences 37: 1265–1270, 1985

    Article  PubMed  CAS  Google Scholar 

  • Biggins JA, Perry EK, McDermott JR, Smith AI, Perry RH, et al. Post mortem levels of thyrotropin-releasing hormone and neurotensin in the Alzheimer’s disease, schizophrenia and depression. Journal of the Neurological Sciences 58: 117–122, 1983

    Article  PubMed  CAS  Google Scholar 

  • Bissette G, Reynolds GP, Kilts CD, Widerlov E, Nemeroff CB. Corticotropin-releasing factor-like immunoreactivity in senile dementia of the Alzheimer type. Journal of the American Medical Association 254: 3067–3069, 1985

    Article  PubMed  CAS  Google Scholar 

  • Bissette G, Widerlov E, Walleus H, Karlsson I, Eklund K, et al. Alterations in cerebrospinal fluid concentrations of somatostatin-like immunoreactivities in neuropsychiatric disorders. Archives of General Psychiatry 43: 1148–1151, 1986

    Article  PubMed  CAS  Google Scholar 

  • Black PM, Ballantine HT, Carr DB, Beal MF, Martin JB. Beta-endorphin and somatostatin concentrations in the ventricular cerebrospinal fluid of patients with affective disorder. Biological Psychiatry 21: 1077–1081, 1986

    Article  PubMed  CAS  Google Scholar 

  • Bradwejn J, Koszycki D, Annable L, Covetoux du Tertre A, Reines S, et al. A dose-ranging study of the behavioural and cardiovascular effects of CCK-tetrapeptide in panic disorder. Biological Psychiatry 32: 903–912, 1992

    Article  PubMed  CAS  Google Scholar 

  • Bruyn GW. Huntington’s chorea: historical, clinical and laboratory synopies. In Vinken & Bruyn (Eds) Handbook of clinical neurology, Vol. 6, pp. 399–403, North-Holland, Amsterdam, 1968

    Google Scholar 

  • Candy JM, Gascoigne AD, Biggins JA, Smith AI, Perry RH, et al. Somatostatin immunoreactivity in cortical and some subcortical regions in Alzheimer’s disease. Journal of the Neurological Sciences 71: 315–323, 1985

    Article  PubMed  CAS  Google Scholar 

  • Chan-Palay V, Lang W, Haesler U, Kohler C, Yasargil G. Distribution of altered hippocampal neurons and axons immunoreactivity with antisera against neuropeptide Y in Alzheimer’s-type dementia. Journal of Comparative Neurology 248: 376–394, 1986

    Article  PubMed  CAS  Google Scholar 

  • Charlton BG, Cheetham SC, Horton RW, Katona CLE, Crompton MR, et al. Corticotropin-releasing immunoreactivity in post-mortem brains from depressed suicides. Journal of Psychopharmacology 2: 13–18, 1988a

    Article  PubMed  CAS  Google Scholar 

  • Charlton BG, Leake A, Wright C, Fairbairn AF, McKeith IG, et al. Somatostatin content and receptors in the cerebral cortex of depressed and control subjects. Journal of Neurology, Neurosurgery and Psychiatry 51: 719–721, 1988b

    Article  CAS  Google Scholar 

  • Conte-Devolx B, Grino M, Nieoullon A, Javoy-Agid F, Castanas E, et al. Corticoliberin, somatocrinin and amine contents in normal and Parkinsonian human hypothalamus. Neuroscience Letters 56: 217–222, 1985

    Article  PubMed  CAS  Google Scholar 

  • Cramer H, Kohler J, Oepen G, Schomburg G, Schroter E. Huntington’s chorea - measurement of somatostatin, substance P and cyclic nucleotides in the cerebrospinal fluid. Journal of Neurology 225: 183–187, 1981

    Article  PubMed  CAS  Google Scholar 

  • Cramer H, Schaudt D, Rissler K, Strubel D, Warter JM, et al. Somatostatin-like immunoreactivity and substance P-like immunoreactivity in the CSF of patients with senile dementia of Alzheimer-type, multi-infarct syndrome and communicating hydrocephalus. Journal of Neurology 245: 1–6, 1985

    Google Scholar 

  • Crawley JN, Olschowska JA, Diz DI, Jacobowitz DM. Behavioural investigation of the co-existence of substance P, corticotropin-releasing factor and acetylcholinesterase in lateral dorsal tegmental neurons projecting to the medial frontal cortex of the rat. Peptides 6: 891–901, 1985

    Article  PubMed  CAS  Google Scholar 

  • Crystal HA, Davis P. Cortical substance P-like immunoreactivity in cases of Alzheimer’s disease and senile dementia of the Alzheimer type. Journal of Neurochemistry 38: 1781–1784, 1982

    Article  PubMed  CAS  Google Scholar 

  • Davies CA, Morroll DR, Prinja D, Mann DMA, Gibbs A. A quantitative assessment of somatostatin-like and neuropeptide Y-like immunostained cells in the frontal and temporal cortex of patients with Alzheimer’s disease. Journal of the Neurological Sciences 96: 59–73, 1990

    Article  PubMed  CAS  Google Scholar 

  • Davies J, Dray A. Substance P in the substantia nigra. Brain Research 107: 623–627, 1976

    Article  PubMed  CAS  Google Scholar 

  • Davies KL, Davidson M, Yang RK, Davies BM, Siever LJ, et al. CSF somatostatin in Alzheimer’s disease, depressed patients, and control subjects. Biological Psychiatry 24: 710–712, 1988

    Article  Google Scholar 

  • Davies P. An update on the neurochemistry of Alzheimer’s disease. In Mayeux & Rosen (Eds) The dementias: advances in neurology, Vol. 38, pp. 75–86, Raven Press, New York, 1983

    PubMed  CAS  Google Scholar 

  • Davies P, Katzman R, Terry RD. Reduced somatostatin-like immunoreactivity in cases of Alzheimer’s disease and Alzheimer senile dementia. Nature 288: 279–280, 1980

    Article  PubMed  CAS  Google Scholar 

  • Dawbarn D, DeQuidt ME, Emson PC. Survival of basal ganglia Neuropeptide Y-somatostatin neurones in Huntington’s disease. Brain Research 340: 251–260, 1985

    Article  PubMed  CAS  Google Scholar 

  • Dawbarn D, Rossor MN, Mountjoy CQ, Roth M, Emson PC. Decreased somatostatin immunoreactivity but not neuropeptide Y immunoreactivity in cortex in senile dementia of Alzheimer type. Neuroscience Letters 70: 154–159, 1986

    Article  PubMed  CAS  Google Scholar 

  • De Bellis MD, Gold PW, Geracioti TD, Listwak SJ, Kling MA. Association of fluoxetine treatment with reductions in CSF concentrations of corticotropin-releasing hormone and arginine vasopressin in patients with major depression. American Journal of Psychiatry 150: 655–657, 1993

    Google Scholar 

  • De Souza EB, Whitehouse PJ, Kuhar MJ, Price DL, Vale WW. Reciprocal changes in corticotropin releasing factor (CRF)-like immunoreactivity and CRF receptors in cerebral cortex of Alzheimer’s disease. Nature 319: 593–595, 1986

    Article  PubMed  Google Scholar 

  • DeWied D. Central actions of neurohypophyseal hormones. In Cross & Leng (Eds) Neurohypothysis: structure, function and control, Progress in brain research, Vol. 60, pp. 151–159, Elsevier, Amsterdam, 1983

    Google Scholar 

  • Dupont E, Christensen SE, Hansen AP, Olivarius B, Orskov H, et al. Low cerebrospinal fluid somatostatin in Parkinson’s disease: an irreversible abnormality. Neurology 32: 312–314, 1982

    Article  PubMed  CAS  Google Scholar 

  • Emson PC, Arregui A, Clement-Jones V, Sandberg BEB, Rossor M. Regional distribution of methionine-enkephalin and substance P-like immunoreactivity in normal brain and in Huntington’s disease. Brain Research 199: 147–160, 1980a

    Article  PubMed  CAS  Google Scholar 

  • Emson PC, Fahrenkrug J, Spokes EGS. Vasoactive intestinal polypeptide (VIP): distribution in normal human and in Huntington’s disease. Brain Research 173: 174–178, 1979

    Article  PubMed  CAS  Google Scholar 

  • Emson PC, Lindvall O. Neuroanatomical aspects of neurotransmitters affected in Alzheimer’s disease. British Medical Bulletin 42: 57–62, 1986

    PubMed  CAS  Google Scholar 

  • Emson PC, Rehfeld JF, Langevin H, Rossor M. Reductions in cholecystokinin-like immunoreactivity in the basal ganglia in Huntington’s disease. Brain Research 198: 497–500, 1980b

    Article  PubMed  CAS  Google Scholar 

  • Epelbaum J, Agid-Javoy F, Enjolbert A, Krantic S, Kordon C, et al. Somatostatin concentrations and binding sites in human frontal cortex are differentially affected in Parkinson’s disease associated dementia and progressive supranuclear palsy. Journal of the Neurological Sciences 87: 167–174, 1988

    Article  PubMed  CAS  Google Scholar 

  • Epelbaum J, Ruberg M, Moyse E, Javoy-Agid F, Dubois B, et al. Somatostatin and dementia in Parkinson’s disease. Brain Research 278: 376–379, 1983

    Article  PubMed  CAS  Google Scholar 

  • Facchinetti F, Nappi G, Petraglia F, Martignoni E, Sinforiani E, et al. Central ACTH deficit in degenerative and vascular dementia. Life Sciences 35: 1691–1697, 1984

    Article  PubMed  CAS  Google Scholar 

  • Ferrante RJ, Kowall NW, Beal MF, Martin JB, Richardson EP, et al. Selective sparing of a class of striatal neurones in Huntington’s disease. Science 230: 561–563, 1985

    Article  PubMed  CAS  Google Scholar 

  • Ferrero P, Benna P, Costa P, Tarenzi L, Baggio G, et al. Diazepam binding inhibitor-like immunoreactivity (DBI-LI) in human CSF: correlations with neurological disorders. Journal of the Neurological Sciences 87: 327–349, 1988

    Article  PubMed  CAS  Google Scholar 

  • Ferrier IN, Cross AJ, Johnson JA, Roberts GW, Crow TJ, et al. Neuropeptides in Alzheimer type dementia. Journal of the Neurological Sciences 62: 159–170, 1983

    Article  PubMed  CAS  Google Scholar 

  • Ferrier IN, Leake A. Peptides in the neocortex in Alzheimer’s disease and aging. Psychoneuroendocrinology 15: 89–95, 1990

    Article  PubMed  CAS  Google Scholar 

  • France RD, Urban B, Krishnan KRR, Bissette G, Banki CM, et al. CSF corticotropin-releasing factor-like immunoreactivity in chronic pain patients with and without major depression. Biological Psychiatry 23: 86–88, 1988

    Article  PubMed  CAS  Google Scholar 

  • Francis PT, Bowen DM. Relevance of reduced concentrations of somatostatin in Alzheimer’s disease. Biochemical Society Transactions 13: 170–171, 1985

    CAS  Google Scholar 

  • Gaillard AWK, Varey CA. Some effects on an ACTH 4-9 analogue (Org 2766) on human performance. Physiological Behaviour 23: 79–84, 1979

    Article  CAS  Google Scholar 

  • Gale JS, Bird ED, Spokes EGS, Iversen LL, Jessell T. Human brain substance P: distribution in controls and Huntington’s chorea. Journal of Neurochemistry 30: 633–643, 1978

    Article  PubMed  CAS  Google Scholar 

  • Gattaz WF, Rissler K, Gattaz D, Cramer H. Effects of haloperidol on somatostatin-like immunoactivity in the CSF of schizophrenic patients. Psychiatry Research 17: 1–6, 1986

    Article  PubMed  CAS  Google Scholar 

  • Gerner RH, Yamada T. Altered neuropeptide concentrations in cerebrospinal fluid of psychiatry patients. Brain Research 238: 298–302, 1982

    Article  PubMed  CAS  Google Scholar 

  • Gjerris A. Do concentrations of neurotransmitters in lumbar CSF reflect cerebral dysfunction in depression. Acta Psychiatrica Scandinavica 78(Suppl. 345): 21–24, 1988

    Google Scholar 

  • Gjerris A, Rafaelsen OJ, Sorensen AS, Bryld EB, Lykke-Olesen L, et al. Cholecystokinin and other neuropeptides in the cerebrospinal fluid (CSF) in psychiatric disorders. Nordia Psykiatria Tidsskr 39(Suppl. 11): 45–49, 1985

    Article  Google Scholar 

  • Gold PW, Chrousos GP, Kellner C, Post R, Roy A, et al. Psychiatric implications of basic and clinical studies with corticotropin-releasing factor. Americal Journal of Psychiatry 141: 619–627, 1984

    CAS  Google Scholar 

  • Gold PW, Robertson GL, James MD, Ballenger JC, Goodwin FK, et al. Neurohypophysial function in affective illness. Psychopharmacology Bulletin 19: 426–431, 1983

    PubMed  CAS  Google Scholar 

  • Gomez S, Puymirat J, Valade P, Davous P, Rondot P, et al. Patients with Alzheimer’s disease show an increased content of 15K dalton somatostatin precursor and a lowered level of tetradecapeptide in their cerebrospinal fluid. Life Sciences 39: 623–627, 1986

    Article  PubMed  CAS  Google Scholar 

  • Goto S, Hirano A, Matsumoto S. Met-enkephalin immunoreactivity in the basal ganglia in Parkinson’s disease and striatonigral degeneration. Neurology 40: 1051–1056, 1990

    Article  PubMed  CAS  Google Scholar 

  • Graf MV, Kastin AJ. Delta-sleep-inducing peptide (DSIP): an update. Peptides 7: 1165–1187, 1986

    Article  PubMed  CAS  Google Scholar 

  • Grafe MR, Forno LS, Eng LF. Immunocytochemical studies of substance P and met-enkephalin in the basal ganglia and substantia nigra in Huntington’s, Parkinson’s and Alzheimer’s diseases. Neuropathology and Experimental Neurology 44: 47–59, 1985

    Article  CAS  Google Scholar 

  • Grigoriadis DE, Struble RG, Price DL, DeSouza EB. Normal pattern of labelling of cerebral cortical corticotropin-releasing factor (CRF) receptors in Alzheimer’s disease: evidence from chemical cross-linking studies. Neuropharmacology 28: 761–764, 1989

    Article  PubMed  CAS  Google Scholar 

  • Gusella JF, Wenler NS, Connenlly PM, Naylor SL, Anderson MA, et al. A polymorphic DNA marker genetically linked to Huntington’s disease. Nature 306: 234–238, 1983

    Article  PubMed  CAS  Google Scholar 

  • Hansen L, Sulman D, Galasko D, Masliah E, Katzman R, et al. The Lewy body variant of Alzheimer’s disease: a clinical and pathologic entity. Neurology 40: 1–8, 1990

    Article  PubMed  CAS  Google Scholar 

  • Harmar AJ. Neuropeptides. In Fluckiger et al. (Eds) Basic and clinical aspects of neuroscience, Vol. 2, pp. 17–26, Springer-Verlag, Berlin, 1987

    Article  CAS  Google Scholar 

  • Hays SE, Paul SM. CCK receptors and human neurological disease. Life Sciences 31: 319–322, 1982

    Article  PubMed  CAS  Google Scholar 

  • Henderson VW, Finch CE. The neurobiology of Alzheimer’s disease. Journal of Neurosurgery 70: 335–353, 1989

    Article  PubMed  CAS  Google Scholar 

  • Henderson VW, Roberts E, Wimer C, Bardolph C, Chui HC, et al. Multicenter trial of naloxone in Alzheimer’s disease. Annals of Neurology 25: 404–406, 1989

    Article  PubMed  CAS  Google Scholar 

  • Hiller JM, Itzhak Y, Simon EJ. Selective changes in μ, δ and K opioid receptor binding in certain limbic regions of the brain in Alzheimer’s disease patients. Brain Research 406: 17–23, 1987

    Article  PubMed  CAS  Google Scholar 

  • Hokfelt T, Rehfeld JF, Skirboll L, Ivenark B, Goldstein M, et al. Evidence for coexistence of dopamine and CCK in meso-limbic neurones. Nature 285: 476–478, 1980

    Article  PubMed  CAS  Google Scholar 

  • Iacono RP, Sandyk R. Alzheimer’s disease and the hypothalamus and intrinsic opioid system. International Journal of Neuroscience 32: 711–714, 1987

    Article  Google Scholar 

  • Iadarola MJ, Mouradian MM. Decrease in a proenkephalin peptide in cerebrospinal fluid in Huntington’s disease and progressive supranuclear palsy. Brain Research 479; 397–401, 1989

    Article  PubMed  CAS  Google Scholar 

  • Ikeda M, Dewar D, McCulloch J. Preservation of [125I]galanin binding sites despite loss of cholinergic neurones to the hippocampus in Alzheimer’s disease. Brain Research 568: 303–306, 1991

    Article  PubMed  CAS  Google Scholar 

  • Javoy-Agid F, Grouselle D, Tixier-Vidal A, Agid Y. Thyrotropin releasing hormone in brain of patients with Parkinson’s disease. Neuropeptides 3: 405–410, 1983

    Article  PubMed  CAS  Google Scholar 

  • Jegou S, Javoy-Agid F, Delbende C, Tranchand-Bunel D, Coy DH, et al. Regional distribution of vasoactive intestinal peptide in brains from normal and Parkinsonian subjects. Neuropeptides 9: 787–793, 1988

    CAS  Google Scholar 

  • Jolkkonen J, Helkala EL, Kutvonen R, Lehtinen M, Riekkinen PJ. Vasopressin levels in CSF of Alzheimer’s patients: correlations with monamine metabolites and neuropsychological test performance. Psychoneuroendocrinology 14: 89–95, 1989

    Article  PubMed  CAS  Google Scholar 

  • Jolkkonen JT, Soininen HS, Riekkinen PJ. β-Endorphin-like immunoreactivity in cerebrospinal fluid of patients with Alzheimer’s disease and Parkinson’s disease. Journal of the Neurological Sciences 77: 153–159, 1987

    Article  PubMed  CAS  Google Scholar 

  • Jones EG, Hendry SHC. Colocalization of GABA and neuropeptides in neocortical neurons. Trends in Neurosciences 9: 71–76, 1986

    Article  CAS  Google Scholar 

  • Jost S, Reuner C, Mohadjo M, Mundinger F, Cramer H. Ventricular fluid neuropeptides in Parkinson’s disease. Levels and distribution of somatostatin-like immunoreactivity. Neuropeptides 15: 219–225, 1990

    Article  PubMed  CAS  Google Scholar 

  • Kanazaura J, Sasaki H, Muramoto O, Matsushita M, Mizutani T, et al. Studies on neurotransmitter markers and striatal neuronal cell density in Huntington’s disease and dentatorubro-pallidoluysian atropy. Journal of the Neurological Sciences 70: 151–165, 1985

    Article  Google Scholar 

  • Kaija H, Tanaka K, Takeuchi K, Morita K, Adachi S, et al. Decreased level of β-endorphin-like immunoreactivity in cerebrospinal fluid of patients with senile dementia of Alzheimer type. Life Sciences 33: 1039–1043, 1983

    Article  Google Scholar 

  • Karlsson I, Widerlov E, Melin EV, Gottfries CG, Wallin A, et al. Changes of CSF neuropeptides after environmental stimulation in dementia. Nordia Psykiatria Tidsskr 30(Suppl. 11): 75–81, 1985

    Article  Google Scholar 

  • Kelley M, Kowall N. Corticotropin-releasing factor immunoreactivity neurons persist throughout the brain in Alzheimer’s disease. Brain Research 501: 392–396, 1989

    Article  PubMed  CAS  Google Scholar 

  • Kirkegaard C, Faber J, Hummer L, Ragowski P. Increased levels of TRH is cerebrospinal fluid from patients with endogenous depression. Psychoneuroendocrinology 4: 227–235, 1979

    Article  PubMed  CAS  Google Scholar 

  • Kitayama I, Janson AM, Cintra A, Fuxe K, Agnati LF, et al. Effects of chronic imipramine treatment on glucocorticoid receptor immunoreactivity in various regions of the rat brain. Journal of Neural Transmission 73: 191–203, 1988

    Article  PubMed  CAS  Google Scholar 

  • Krieger DT. Brain peptides: what, where and why? Science 222: 975–985, 1983

    Article  PubMed  CAS  Google Scholar 

  • Kulmala HK. Immunocytochemical localization of enkephalin-like immunoreactivity in neurons of human hippocampal formation: Effects of ageing and Alzheimer’s disease. Neuropathology and Applied Neurobiology 11: 105–115, 1985

    Article  PubMed  CAS  Google Scholar 

  • Leake A, Perry EK, Perry RH, Fairbairn AF, Ferrier IN. Cortical concentrations of corticotropin releasing hormone and its receptor in Alzheimer type dementia and major depression. Biological Psychiatry 28: 603–608, 1990

    Article  PubMed  CAS  Google Scholar 

  • Leake A, Perry EK, Perry RH, Jabeen S, Fairbairn AF, et al. Neocortical concentrations of neuropeptides in senile dementia of the Alzheimer and Lewy body type. Comparison with Parkinson’s disease and severity correlations. Biological Psychiatry 29: 357–364, 1991

    Article  PubMed  CAS  Google Scholar 

  • Leonard S, Logel J, Luthman D, Casanova M, Kirch D, et al. Biological stability of mRNA isolated from human postmortem brain collections. Biological Psychiatry 33: 456–466, 1993

    Article  PubMed  CAS  Google Scholar 

  • Licinio J, Gold PW. Role of corticotropin releasing hormone 41 in depressive illness. In Grossman (Ed.) Clinical endocrinology and metabolism: psychoneuroendocrinology, Vol. 5, pp. 51–58, Balliere Tindall, London, 1991

    CAS  Google Scholar 

  • Llorens-Cortes C, Javoy-Agid F, Agid Y, Tawuet H, Schwartz C. Enkephalinergic markers in substantia nigra and caudate nucleus for Parkinsonian subjects. Journal of Neurochemistry 43: 874–877, 1985

    Article  Google Scholar 

  • Martignoni E, Petraglia F, Costa A, Bono G, Genazzani AR, et al. Dementia of the Alzheimer type and hypothalamus-pituitary-adrenocortical axis: changes in cerebrospinal fluid corticotropin releasing factor and plasma Cortisol levels. Acta Neurologica Scandinavica 81: 452–456, 1990

    Article  PubMed  CAS  Google Scholar 

  • Matussek N, Hoehe M. Investigations with the specific μ-opiate receptor fentanyl in depressive patients. Growth hormone, prolactin, Cortisol, noradrenaline and euphoric responses. Neuropsychobiology 21: 1366–1375, 1989

    Article  Google Scholar 

  • Mauborgne A, Javoy-Agid F, Legrand JC, Agid Y, Cesselin F. Decrease of substance P-like immunoreactivity in the substantia nigra and pallidum of Parkinsonian brains. Brain Research 268: 167–170, 1983

    Article  PubMed  CAS  Google Scholar 

  • May C, Rapoport SI, Tomai BS, Chrousos GP, Gold PW. Cerebrospinal fluid concentrations of corticotropin releasing hormone (CRH) and corticotropin (ACTH) are reduced in patients with Alzheimer’s disease. Neurology 37: 535–538, 1987

    Article  PubMed  CAS  Google Scholar 

  • Mazurek MF, Beal MF, Bird ED, Martin JB. Vasopressin in Alzheimer’s disease: a study of postmortem brain concentrations. Annals of Neurology 20: 665–670, 1986a

    Article  PubMed  CAS  Google Scholar 

  • Mazurek MF, Growdon JH, Beal MF, Martin JB. CSF vasopressin concentration is reduced in Alzheimer’s disease. Neurology 36: 1133–1137, 1986b

    Article  PubMed  CAS  Google Scholar 

  • Mellow AM, Aronson SM, Giordani B, Berent S. Combined thyrotropin-releasing hromone (TRH)-physostigmine infusions in Alzheimer’s disease (AD): initial results with a peptide-enhancement strategy. Biological Psychiatry 31: 153A, 1992

    Google Scholar 

  • Miller TP, Fong K, Tinklenberg JR. An ACTH 4-9 analog (Org 2766) and cognitive performance: high dose efficacy and safety in dementia of the Alzheimer’s type. Biological Psychiatry 33: 307–309, 1993

    Article  PubMed  CAS  Google Scholar 

  • Molcho A, Parsons B, Kassir S, Stanley M. An autoradiographic study of changes in opioid receptors in brains of suicide victims. Biological Psychiatry 31: 101A, 1992

    Google Scholar 

  • Morrison JH, Rogers J, Scherr S, Benoit R, Bloom FE. Somatostatin immunoreactivity in neuritic plaques of Alzheimer patients. Nature 314: 90–92, 1985

    Article  PubMed  CAS  Google Scholar 

  • Mouradian MM, Farah JM, Mohr E, Fabbrini G, O’Donohue EL, et al. Spinal fluid CRF reduction in Alzheimer’s disease. Neuropeptides 8: 393–400, 1986

    Article  PubMed  CAS  Google Scholar 

  • Naber RD, Pickar D, Post RM, VanKammen DP, Waters RN, et al. Endogenous opiate receptor and beta-endorphin immunoreactivity in CSF of psychiatric patients and normal volunteers. American Journal of Psychiatry 138: 1457–1462, 1981

    PubMed  CAS  Google Scholar 

  • Nakajima T, Ono Y, Kato A, Maeda J, Ohe T. Y-29794 - a non-peptide prolyl endopeptidase inhibitor that can penetrate into the brain. Neuroscience Letters 141: 156–160, 1992

    Article  PubMed  CAS  Google Scholar 

  • Nappi G, Sinforiani E, Facchinetti F, Petraglia F, Bono G, et al. Opioids, aging brain and dementia. In Nappi et al. (Eds) Neurodegenerative disorders: the role played by endotoxins and xenobiotics, pp. 32–42, Raven, New York, 1988a

    Google Scholar 

  • Nappi G, Sinforiani E, Martignoni E, Petraglia F, Facchinetti F, et al. Aging brain and dementias: changes in central opioids. European Neurology 28: 217–220, 1988b

    Article  PubMed  CAS  Google Scholar 

  • Nemeroff CB, Owens JM, Bissette G, Andorn AC, Stanley M. Reduced corticotropin releasing factor binding sites in the frontal cortex of suicide victims. Archives of General Psychiatry 45: 577–579, 1988

    Article  PubMed  CAS  Google Scholar 

  • Nemeroff CB, Widerlov E, Bissette G, Walleus H, Karlsson I, et al. Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science 226: 1342–1344, 1984

    Article  PubMed  CAS  Google Scholar 

  • Nemeroff CB, Youngblood WW, Manberg PJ, Prange AJ, Kizer JS. Regional brain concentrations of neuropeptides in Huntington’s chorea and schizophrenia. Science 221: 972–975, 1983

    Article  PubMed  CAS  Google Scholar 

  • Nishimura T, Niigaura H, Caeabeurs R, Tada K, Karguchi K. In Iizuka (Ed.) Pathogenesis and therapy of senile dementia, pp. 97–106, Koseisho, Tokyo, 1986

  • Perry EK. The cholinergic hypothesis - ten years on. British Medical Bulletin 42: 63–69, 1986a

    PubMed  CAS  Google Scholar 

  • Perry EK, Blessed G, Tomlinson BE, Perry RH, Crow TJ, et al. Neurochemical activities in human temporal lobe related to aging and Alzheimer type changes. Neurobiology of Aging 2: 251–256, 1981

    Article  PubMed  CAS  Google Scholar 

  • Perry EK, Perry RH. Human brain neurochemistry - some post-mortem problems. Life Science 33: 1733–1743, 1983

    Article  CAS  Google Scholar 

  • Perry EK, Perry RH, Tomlinson BE. The influence of agonal status on some neurochemical activities of postmortem brain tissue. Neuroscience Letters 29: 303–307, 1982

    Article  PubMed  CAS  Google Scholar 

  • Perry RH. Recent advances in neuropathology. British Medical Bulletin 42: 34–41, 1986b

    PubMed  CAS  Google Scholar 

  • Perry RH, Irving D, Blessed G, Perry EK, Fairbairn AF. Clinically and neuropathologically distinct form of dementia in the elderly. Lancet 1: 166, 1989

    Article  PubMed  CAS  Google Scholar 

  • Perry RH, Irving D, Blessed G, Fairbairn AF, Perry EK. Senile dementia of Lewy body type. A clinically and neuropathologically distinct form of Lewy body dementia in the elderly. Journal of the Neurological Sciences 95: 119–139, 1990

    Article  PubMed  CAS  Google Scholar 

  • Pezzoli G, Parerai AE, DiGiulio A, Longo A, Passerini D, et al. Methionine-enkephalin, substance P, and homovanillic acid in the CSF of Parkinsonian patients. Neurology 34: 516–519, 1984

    Article  PubMed  CAS  Google Scholar 

  • Pierotti AR, Harmar AJ, Simpson J, Yates CM. High molecular-weight forms of somatostatin are reduced in Alzheimer’s disease and Down’s syndrome. Neuroscience Letters 63: 141–146, 1986

    Article  PubMed  CAS  Google Scholar 

  • Pique L, Jegou S, Bertagna X, Javoy-Agid F, Sewin D, et al. Proopiomelanocortin peptides in the human hypothalamus: comparative study between normal subjects and Parkinson patients. Neuroscience Letters 54: 141–146, 1985

    Article  PubMed  CAS  Google Scholar 

  • Pomara N, Singh RR, Deptula D, LeWitt PA, Bissette G, et al. CSF corticotropin-releasing factor in Alzheimer’s disease: its relationship to severity of dementia and monoamine metabolites. Biological Psychiatry 26: 500–504, 1989

    Article  PubMed  CAS  Google Scholar 

  • Powers RE, Walker LC, De Souza EB, Vale WW, Struble RG, et al. Immunohistochemical study of neurons containing corticotropin-releasing factor in Alzheimer’s disease. Synapse 1: 405–410, 1987

    Article  PubMed  CAS  Google Scholar 

  • Rainero I, Kaye JA, May C, Durso R, Katz DI, et al. α-Melanocyte-stimulating hormone-like immunoreactivity is increased in cerebrospinal fluid of patients with Parkinson’s disease. Archives of Neurology 45: 1224–1227, 1988

    Article  PubMed  CAS  Google Scholar 

  • Raskind MA, Peskind ER, Lampe TH, Risse SC, Taborsky GJ, et al. Cerebrospinal fluid vasopressin, oxytocin, somatostatin and β-endorphin in Alzheimer’s disease. Archives of General Psychiatry 43: 382–388, 1986

    Article  PubMed  CAS  Google Scholar 

  • Reinikainen KJ, Riekkinen PJ, Jolkkonen J, Kosma VM, Soininen H. Decreased somatostatin-like immunoreactivity in cerebral cortex and cerebrospinal fluid in Alzheimer’s disease. Brain Research 402: 103–108, 1987

    Article  PubMed  CAS  Google Scholar 

  • Risch SC, Kalin NH. Dysregulated CSF ‘POMC’ peptides in depression. Biological Psychiatry 25: 407, 1989

    Article  Google Scholar 

  • Roberts GW, Crow TJ, Polak JM. Location of neuronal tangles in somatostatin neurones in Alzheimer’s disease. Nature 314: 92–94, 1985

    Article  PubMed  CAS  Google Scholar 

  • Rossor MN, Emson PC, Mountjoy CQ, Roth M, Iversen LL. Reduced amounts of immunoreactive somatostatin in the temporal cortex in senile dementia of Alzheimer type. Neuroscience Letters 20: 373–377, 1980a

    Article  PubMed  CAS  Google Scholar 

  • Rossor MN, Fahrenkurg J, Emson P, Mountjoy C, Iversen LL, et al. Reduced cortical choline acetyltransferase activity in senile dementia of Alzheimer type is not accompanied by changes in vasoactive intestinal polypeptide. Brain Research 201: 249–253, 1980b

    Article  PubMed  CAS  Google Scholar 

  • Rossor MN, Hunt SP, Iversen LL, Bannister R, Hawthorn J, et al. Extrahypothalamic vasopressin is unchanged in Parkinson’s disease and Huntington’s disease. Brain Research 253: 341–343, 1982a

    Article  PubMed  CAS  Google Scholar 

  • Rossor M, Iversen LL. Non-cholinergic neurotransmitter abnormalities in Alzheimer’s disease. British Medical Bulletin 42: 70–74, 1986

    PubMed  CAS  Google Scholar 

  • Rossor MN, Iversen LL, Hunt SP, Hawthorn J, Arg VTY, et al. Vasopressin in human brain. In Baertschi & Drieffus (Eds) Neuroendocrinology of vasopressin, corticoliberin and opiomelanocortins, pp. 61–71, Academic Press, London, 1982b

    Google Scholar 

  • Rossor MN, Rehfeld JF, Emson PC, Mountjoy CQ, Iversen LL. Normal cortical concentrations of cholecystokinin-like immunoreactivity with reduced choline acetyltransferase activity in senile dementia of the Alzheimer type. Life Sciences 29: 405–410, 1981

    Article  PubMed  CAS  Google Scholar 

  • Roy A, Pickar D, Paul S, Doran AR, Chrousos GP, et al. CSF corticotropin-releasing hormone in depressed patients and normal control subjects. American Journal of Psychiatry 144: 641–645, 1987

    PubMed  CAS  Google Scholar 

  • Rubinow DR. Cerebrospinal fluid somatostatin and psychiatric illness. Biological Psychiatry 21: 341–365, 1986

    Article  PubMed  CAS  Google Scholar 

  • Rubinow DR, Post RM, Davis CL, Doran AR. Somatostatin and GHRH: mood and behavioural regulation. In Nerozzi et al. (Eds) Hypothalamic dysfunction in neuropsychiatry disorders. Advances in Biochemical Psychopharmacology, Vol. 43, pp. 137–152, Raven Press, New York, 1987

    CAS  Google Scholar 

  • Sachar EJ, Hellman L, Roffwarg HP, Halpern FS, Fukuchima DK, et al. Disrupted 24 hour patterns of cortical secretion in psychotic depression. Archives of General Psychiatry 28: 19–24, 1973

    Article  PubMed  CAS  Google Scholar 

  • Sahgal A, Keith AB, Wright C, Edwardson JA. Failure of vasopressin to enhance memory in a passive avoidance task in rats. Neuroscience Letters 28: 87–92, 1982

    Article  PubMed  CAS  Google Scholar 

  • Sakamoto S, Goto S, Ito H, Hirano A. Striosomal organization of substance P-like immunoreactivity in parkinsonian patients. Neurology 42: 1071–1075, 1992

    Article  PubMed  CAS  Google Scholar 

  • Sakurada T, Alufuzoff I, Winblad B, Nordberg A. Substance P-like immunoreactivity, choline acetyltransferase activity and cholinergic muscarinic receptors in Alzheimer’s disease and multi-infarct dementia. Brain Research 521: 329–333, 1990

    Article  PubMed  CAS  Google Scholar 

  • Serby M, Resnick R, Jordan B, Adler J, Cerwin J, et al. Naltrexone and Alzheimer’s disease. Progress in Neuro-Psychopharmacology and Biological Psychiatry 10: 587–590, 1986

    Article  PubMed  CAS  Google Scholar 

  • Sharpless NS, Thal LJ, Perlow MJ, Tabaddor K, Waltz JM, et al. Vasoactive intestinal peptide in cerebrospinal fluid. Peptides 5: 429–433, 1984

    Article  PubMed  CAS  Google Scholar 

  • Sorensen PS, Gjerris A, Hammer M. Cerebrospinal fluid vasopressin in neurological and psychiatric disorders. Journal of Neurology, Neurosurgery and Psychiatry 48: 50–57, 1985

    Article  CAS  Google Scholar 

  • Sourkes TL. Parkinson’s disease other disorders of the basal ganglia. In Siegel et al. (Eds) Basic neurochemistry, 3rd ed., pp. 719–733, Little Brown, Boston, 1981

    Google Scholar 

  • Spindel ER, Wurtman RJ, Bird ED. Increased TRH content of the basal ganglia in Huntington’s disease. New England Journal of Medicine 303: 1235–1236, 1980

    PubMed  CAS  Google Scholar 

  • Studler JM, Javoy-Agid F, Cesselin F, Legrand JG, Agid Y. CCK-8 immunoreactivity distribution in human brain: selective decrease in the substantia nigra from Parkinsonian patients. Brain Research 243: 176–179, 1982

    Article  PubMed  CAS  Google Scholar 

  • Sunderland T, Rubinow DR, Tariot PN, Cohen RM, Newhouse PA, et al. CSF somatostatin in patients with Alzheimer’s disease, older depressed patients with age-matched control subjects. American Journal of Psychiatry 144: 1313–1316, 1987

    PubMed  CAS  Google Scholar 

  • Suranji-Cadotte BE, Dam TV, Quinon R. Antidepressant-anxiolytic interaction: decreased density of benzodiazepines receptors in rat brain following chronic administration of antidepressant drugs. European Journal of Pharmacology 106: 673–675, 1985

    Article  Google Scholar 

  • Taquet H, Javoy-Agid F, Giraud P, Legrand JC, Agid Y, et al. Dynorphin levels in Parkinsonian patients: Leus-enkephalin production from either proenkephalin A or prodynorphin in human brain. Brain Research 341: 390–392, 1985

    Article  PubMed  CAS  Google Scholar 

  • Taquet H, Javoy-Agid F, Hamon M, Legrand JC, Agid Y, et al. Parkinson’s disease affects differently Met 5 and Leu 5-enkephalin in the human brain. Brain Research 280: 379–382, 1983

    Article  PubMed  CAS  Google Scholar 

  • Tenovvo O, Rinne UK, Viljanen MK. Substance P immunoreactivity in the post-mortem Parkinsonian brain. Brain Research 303: 113–116, 1984

    Article  Google Scholar 

  • Terenius L, Wohlstrom A, Agren H. Naloxone (Narcan) treatment in depression: clinical observations and effects of CSF endorphins and monoamine metabolites. Psychopharmacology 54: 31–37, 1977

    Article  PubMed  CAS  Google Scholar 

  • Thal LJ, Sharpless NS, Hirschhorn ID, Horowitz SG, Makman MH. Striatal met-enkephalin concentration increases following nigrostriatal denervation. Biochemical Pharmacology 32: 3297–3301, 1983

    Article  PubMed  CAS  Google Scholar 

  • Tomlinson BE, Corsellis JAN. Ageing and the dementias. In Hume Adams et al. (Eds) Greenfield’s neuropathology, pp. 951–1025, Edward Arnold, London, 1984

    Google Scholar 

  • Tsagarakis S, Holly JMP, Rees LH, Besser GM, Grossman A. Acetylcholine and norepinephrine stimulate the release of corticotropin-releasing factor −41 from the rat hypothalamus. Endocrinology 123: 1962–1969, 1988

    Article  PubMed  CAS  Google Scholar 

  • Tsuji M, Takahashi S, Akazaura S. CSF vasopressin and cyclic nucleotide concentrations in senile dementia. Psychoneuroendocrinology 6: 171–176, 1981

    Article  PubMed  CAS  Google Scholar 

  • Verbanck PMP, Lotstra F, Gilles C, Linkowski P, Mendlewicz J, et al. Reduced cholecystokinin immunoreactivity in the cerebrospinal fluid of patients with psychiatric disorders. Life Sciences 2: 67–72, 1984

    Article  Google Scholar 

  • Veith RC, Raskind MA. The neurobiology of ageing: does it predispose to depression? Neurobiology of Aging 9: 101–107, 1988

    Article  PubMed  CAS  Google Scholar 

  • Weingartner H, Gold P, Ballenger JC, Smallberg SA, Summers R, et al. Effects of vasopressin on human memory functions. Science 211: 601–603, 1981

    Article  PubMed  CAS  Google Scholar 

  • Whitehouse PJ, Vale WW, Zweig RM, Singer HS, Mayeux R, et al. Reductions in corticotropin releasing factor-like immunoreactivity in cerebral cortex in Alzheimer’s disease, Parkinson’s disease, and progressive supranuclear palsy. Neurology 37: 905–909, 1987

    Article  PubMed  CAS  Google Scholar 

  • Whitford CA, Candy JM, Edwardson JA, Perry RH. Cortical somatostatinergic system not affected in Alzheimer’s and Parkinson’s disease. Journal of the Neurological Sciences 86: 13–18, 1988

    Article  PubMed  CAS  Google Scholar 

  • Whitford CA, Court JA, Moses MA, Candy JM. Stability of adenylate cyclase coupling to somatostatin and corticotropin-releasing-factor receptors in frozen post-mortem human cerebral cortex. Biochemistry Society Transactions 17: 205–206, 1989

    CAS  Google Scholar 

  • Widerlov E, Brane GAM, Ekmon R, Kihlgren M, Norberg A, et al. Elevated CSF somatostatin concentrations in demented patients parallel improved psychomotoric function induced by integrity-promoting care. Acta Psychiatria Scandinavica 79: 41–47, 1989

    Article  CAS  Google Scholar 

  • Wikkelso C, Fahrenkrug J, Bloomstand C, Johansson BB. Dementia of different etiologies: vasoactive intestinal polypeptide in CSF. Neurology 35: 592–595, 1985

    Article  PubMed  CAS  Google Scholar 

  • Yates CM, Fink G, Bennie JG, Gordon A, Simpson J, et al. Neurotensin immunoreactivity in post-mortem brain is increased in Down’s syndrome but not in Alzheimer-type dementia. Journal of the Neurological Sciences 67: 327–335, 1985

    Article  PubMed  CAS  Google Scholar 

  • Yates CM, Harmar AJ, Rosie R, Sheward J, Sanchez DE, et al. Thyrotropin-releasing hormone, luteinizing hormone-releasing hormone and substance P immuno-reactivity in postmortem brain cases of Alzheimer-type dementia and Down’s syndrome. Brain Research 258: 45–52, 1983

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. MRC Neurochemical Pathology Unit, Newcastle General Hospital, Westgate Rd, Newcastle upon Tyne, NE4 6BE, England

    Alan Leake & I. Nicol Ferrier

Authors
  1. Alan Leake
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. Nicol Ferrier
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Leake, A., Ferrier, I.N. Alterations in Neuropeptides in Aging and Disease. Drugs & Aging 3, 408–427 (1993). https://doi.org/10.2165/00002512-199303050-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002512-199303050-00003

Keywords

Search

Navigation