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The Italian Journal of Neurological Sciences

, Volume 8, Issue 5, pp 457–463 | Cite as

Alterations of the cerebral capillary bed in the senile dementia of Alzheimer

  • Scheibel A. B. 
Original Articles

Abstract

Brain tissue specimens from 15 patients dying with neuropathologically confirmed clinical diagnoses of senile dementia, Alzheimer type, and 10 approximately age and sex matched elderly patients without signs of senile change, were compared using a group of neurohistological techniques including scanning electron microscopy. In addition to previously described changes in structure of neurons and neuropil, dramatic changes were noted in the capillary bed. Normal cerebral vessels are characterized by smooth contours, the presence of occasional pericytes, and a plexus of pericapillary nerve fibers bearing many varicosities which have been shown to be strongly positive for norepinephrine, acetylcholine, dopamine and several other putative neurotransmitters or neuromodulators. In our series of Alzheimer patients the cerebral vessels were highly irregular in appearance, covered with rounded or conical extrusions (lumps and bumps), and totally lacking in the perivascular plexus of nerve fibers. In about three quarters of the cases studied the vessel walls were perforated by multiple openings of varying sizes, most of which appeared to run through the complete thickness of the thickened basement membrane but did not perforate the endothelial lining of the capillary lumen. The origin and pathogenesis of these changes is still unknown although some of the materials infiltrating the vascular walls appear to contain amyloid. On the basis of presently available evidence, it is suggested that widespread microvascular pathology may be caused by loss of the perivascular neural plexus (denervating microangiopathy) and that this may result in breakdown of the blood brain barrier. It is conceivable that the widespread degeneration characteristic of senile domentia, Alzheimer type, develops secondarily to these structuro-functional alterations in the microvasculature and that the primary target of the Alzheimer process may be located in subcortical nuclei, e.g. locus ceruleus and nucleus basalis of Meynert, which normally supply innervation to the cerebral vessels.

Key-Words

Cerebral capillary bed Alzheimer disease nucleus basalis denervating microangiopathy 

Sommario

Sono stati messi a confronto in questo studio preparati istologici cerebrali di 15 pazienti morti con diagnosi clinica di malattia di Alzheimer e di 10 individui anziani comparabili per età e sesso, morti senza presentare segni clinici di involuzione neuropsichica senile. Oltre alle già note alterazioni della struttura dei neuroni e dei neuropili sono state messe in evidenza importantissime varianti del letto capillare. Infatti, nella nostra serie di malati affetti da malattia di Alzheimer i vasi cerebrali appaiono molto irregolari con ostruzioni coniche o rotonde e sono totalmente privi di fibre nervose del plesso perivascolare. In tre quarti dei casi studiati le pareti vasali apparivano interrotte da soluzioni di continuo di varia ampiezza che interessavano totalmente la spessa membrana basale, mentre risultava indenne l’endotelio. Parte del materiale che infiltrava la parete vasale contiene sostanza amiloide. Sulla base di questi dati si può ipotizzare che questa microangiopatia denervante determini la rottura della barriera emato-encefalica e ciò fa ritenere che il primo bersaglio della malattia di Alzheimer siano il locus ceruleus e il nucleo basale di Meynert che normalmente provvedono alla innervazione dei vasi cerebrali.

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References

  1. [1]
    Bell M.A., Ball M.J.:Morphometric comparison of hippocampal microvasculature in aging and demented people: diameters and densities. Acta Neuropathol. 53: 299–318, 1981.CrossRefPubMedGoogle Scholar
  2. [2]
    Bondareff W., Mountjoy C.O., Roth M.:Loss of neurons of origin of the adrenergic projection to cerebral cortex in senile dementia. Neurology 32: 164–168, 1982.PubMedGoogle Scholar
  3. [3]
    Brayden J.E., Bevan J.A.:Neurogenic muscarinic vasodilatation in the cat. Circ. Res. 56: 205–211, 1985.PubMedGoogle Scholar
  4. [4]
    Edvinssn L.:Functional role of perivascular peptides in the control of cerebral circulation. Trends in Neurosci. 8: 126–131, 1985.Google Scholar
  5. [5]
    Edvinson L., Lindvall M., Nielsen K.C., Owman C.H.:Are brain vessels innervated also by central (non-sympathetic) adrenergic neurons? Brain Res. 63: 469–499. 1973.Google Scholar
  6. [6]
    Glenner G.G.:Current knowledge of amyloid deposits as applied to senile plaques and congophilic angiopathy. Aging NY 7: 493–501, 1978.Google Scholar
  7. [7]
    Glenner G.G., Wong C.W.:Alzheimer’s disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun. 120: 885–890, 1984.CrossRefPubMedGoogle Scholar
  8. [8]
    Goldgaber D., Lerman M.I., McBride O.W., Saffretti U., Gajchusek D.C.:Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer’s Disease. Science 235: 877–880, 1987.PubMedGoogle Scholar
  9. [9]
    Gunn C.G.:Proliferative nature of arteriosclerosis and regulators of metabolism and movement. In: Wolfe, S. (Ed.). The Artery and the Process of Arteriosclerosis, New York, Plenum Press, 56 et seq.; 230 et seq. 1971.Google Scholar
  10. [10]
    Hartman B.K.:The innervation of cerebral blood vessels by central noradrenergic neurons. In: Usden, E., Snyder, S. (Eds.), Frontiers in Catecholamine Research. New York, Pergamon Press, 91–96, 1973.Google Scholar
  11. [11]
    Hassler O.:Vascular changes in senile brains. Acta Neuropathol. (Berlin) 1965; 5: 40–53.CrossRefGoogle Scholar
  12. [12]
    Itakura T., Yamamoto K., Tohyama M., Shimizu N.:Central dual innervation of arterioles and capillaries in the brain. Stroke 8: 360–365.Google Scholar
  13. [13]
    Raichle M.E., Hartman B.K., Eichling J.O., Sharpe L.G.:Central noradrenergic regulation of cerebral blood flow and vascular permeability. Proc. Natl. Acad. Sci.; 72: 3726–3730, 1975.PubMedGoogle Scholar
  14. [14]
    Ravens J.R.:Vascular changes in the human senile brain. In: Cervós-Navarro, J., Betz, E., Eberhardt, G., Ferst, R., Wullenweber, XX (Eds.), Pathology of Cerebrospinal Microcirculation: Vol. 20, Advances in Neurology. New York, Raven Press, 487–501, 1978.Google Scholar
  15. [15]
    Rennels M.L., Nelson E.:Capillary innervation in the mammalian central nervous system. Am. J. Anat.; 144: 233–241, 1975.CrossRefPubMedGoogle Scholar
  16. [16]
    Ccheibel A.B., Duong T., Tomiyasu, U.:Microvascular changes in Alzheimer’s Disease. In: A.B. Scheilbel and A. Websters (Eds.), The Biological Substrates of Alzheimer’s Disease. New York, Academic Press; 177–192, 1986.Google Scholar
  17. [17]
    Scheibel A.B., Fried I.:Age-related changes in the peri-capillary environment. In: Samuel D., Algeri, A., Gershon, S., Grimm, V.E., Toffano, G. (Eds.), Aging of the Brain: Vol. 22, The Aging Series, New York, Raven Press; 81–92, 1983.Google Scholar
  18. [18]
    Scheibel M.E., Lindsay R.D., Romiyasu U., Scheibel A.B.:Progressive dendritic changes in aging human cortex. Exp. Neurol. 47: 392–403, 1975.PubMedGoogle Scholar
  19. [19]
    Scremin O.U., Rovere A.A., Raynald A.C., Giardni A.:Cholinergic control of blood flow in the cerebral cortex of the cat, Stroke; 4: 232–239, 1974.Google Scholar
  20. [20]
    St. George-Hyslop P., Tanzi R.E., Polinsky R.J., Haines J.L., Nee L., Watkins D.C., Myers R.W., Feldman R.G., Pollen D., Drachman D., Gowdon, J., Buni A., Foncin J.F., Salmon D., Frommelt, P., Amaducci L., Sorbi S., Piacentini S., Stewart G.D., Hobbs W.J., Conneally P.M., Gusella J.F.:The genetic defect causing familial Alzheimer’s Disease maps on Chromosome 21. Science; 235: 885–590, 1987.PubMedGoogle Scholar
  21. [21]
    Terry R.D.:Ultrastructural studies in Alzheimer’s presenile dementia. Am. J. Pathol.; 44: 269–281. 1964.PubMedGoogle Scholar
  22. [22]
    Tuke J.B.:On the morbid histology of the brain and spinal cords as observed in the insane. Br. For. Med. Chir. Rev.; 51: 450–460, 1873.Google Scholar
  23. [23]
    Whitehouse P.J., Price D.L., Clark A.W., Coyle J.T., De Long M.R.:Alzheimer’s disease: Evidence for selective loss of cholinergic neurons in the nucleus basalis. An. Neurol. 10: 122–126, 1981.Google Scholar

Copyright information

© Masson Italia Periodici S.r.l. Milano 1987

Authors and Affiliations

  • Scheibel A. B. 
    • 1
    • 2
    • 3
  1. 1.Department of AnatomyU.C.L.A. Medical CenterLos AngelesU.S.A.
  2. 2.Department of PsychiatryU.C.L.A. Medical CenterLos AngelesU.S.A.
  3. 3.Department of the Brain Research InstituteU.C.L.A. Medical CenterLos AngelesU.S.A.

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