Neurodegenerative Changes in Aging and Dementia: A Comparison of Alzheimer and Lewy Body Type Pathology

  • Elaine K. Perry
  • Elizabeth Marshall
  • Anthony Cheng
  • James A. Edwardson
  • Robert H. Perry


Whereas cortical senile plaques are evident in the vast majority of elderly people and as such can be considered part of the “normal” aging process, Lewy bodies are found in the cortex of a very small proportion (<5%) of normal aged (over 70 yr) individuals and may be more specifically disease-associated. Lewy bodies invariably appear in the cortex of elderly patients suffering from a form of dementia that is clinically distinct from Alzheimer’s disease (AD)—Senile Dementia of Lewy Body Type (SDLT). SDLT is part of the spectrum of Lewy body disease (which also includes diffuse Lewy body disease) and is distinguished by the relatively high incidence of mainly visual hallucinations. Although memory impairment (the cardinal feature of AD, also evident in SDLT) may to some degree be an inevitable concomitant of the aging process, hallucinations are not generally associated with normal aging and presumably relate in SDLT to specific disease-related alterations in brain function. At the histological level there is, however, no obvious correlation between the distribution or density of cortical Lewy bodies and the incidence of hallucinations, although at the biochemical level an interesting relationship is apparent. Distinct profiles of cholinergic and monoaminergic transmitter activities were evident in AD and SDLT, particularly with respect to the occurrence of hallucinations in the latter. Thus the presynaptic cholinergic enzyme choline acetyltransferase was significantly lower, whereas pre- and post-synaptic serotonergic activities (5HIAA and 5HT2 receptor binding) were relatively spared in the hallucinating SDLT group compared to AD and the non-hallucinating SDLT group. The concept of an imbalance between serotonin and acetylcholine with relatively hyperactive serotonergic and hypoactive cholinergic activities being associated with hallucinating experiences is consistent with the psychopharmacology of drugs affecting the respective systems. Thus, cholinergic antagonists and selective serotonergic agonists tend to be hallucinogenic, although whether cholinergic agonist or serotonergic (S2) antagonist drug treatments would alleviate hallucinations in SDLT remains to be determined.


Lewy Body Nicotinic Receptor Choline Acetyltransferase Senile Dementia Lewy Body Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Byrne EJ, Lennox G, Lowe J, Godwin-Austen R (1989): Diffuse Lewy body disease: clinical features in 15 cases. J Neurol Neurosurg Psychiat 52:709–717CrossRefGoogle Scholar
  2. Cheetham SC, Crompton MR, Katona CLE, Horton RW (1988): Brain 5HT2 receptor binding in depressed suicide victims. Brain Res 443:272–280CrossRefGoogle Scholar
  3. Fonnum F (1975): A rapid radiochemical method for the determination of choline acetyltransferase. J Neurochem 24:407–409CrossRefGoogle Scholar
  4. Gaspar P, Berger B, Febvret A, Vigny A, Krieger-Poulet M, Borri-Vottattorni C (1987): Tyrosine hydroxy lase-immunoreactive neurons in the human cerebral cortex: a novel catecholaminergic group? Neurosci Lett 80:257–262CrossRefGoogle Scholar
  5. Gibb WRG, Lees AJ (1988): The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson’s disease. J Neurol Neurosurg Psychiat 51:745–752CrossRefGoogle Scholar
  6. Glennon RA, Titeler M, McKenney JD (1984): Evidence for 5HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sci 35:2505–2511CrossRefGoogle Scholar
  7. Goodman LS, Gilman A (1975): The Pharmacological Basis of Therapeutics. New York: MacMillan Publishing CompanyGoogle Scholar
  8. Hansen L, Salmon D, Galaska D, Masliah E, Katzman R, De Teresa R, Thal L, Bay MM, Hofstelter R, Klanber M, Rice V, Butters N, Alford M (1989): The Lewy body variant of Alzheimer’s disease. Neurol 40:1–8Google Scholar
  9. Hauw JJ, Duyckaerts C, Delaere P (1988): Neuropathology of aging and DAT: how can age-related changes be distinguished from those due to disease processes. In: Etiology of Dementia of Alzheimer’s Type, Henderson AS, Henderson JH, eds. Chichester: John Wiley and Sons, pp. 195–212Google Scholar
  10. Kuljis R, Martin-Vasallo P, Peress NS (1989): Lewy bodies in tyrosine hydroxylase synthesizing neurons of the human cerebral cortex. Neurosci Lett 106:49–54CrossRefGoogle Scholar
  11. Marcusson JO, Norgan DG, Winblad B, Finch CG (1984): Serotonin-2 binding sites in human frontal cortex and hippocampus. Selective loss of 2-A sites with age. Brain Res 311:51–56CrossRefGoogle Scholar
  12. Penfield W, Jasper H (1954): Epilepsy and the Functional Anatomy of the Human Brain. London: J and A ChurchillGoogle Scholar
  13. Perry EK, Perry RH (1988): Aging and dementia: neurochemical and neuropatho-logical comparisons. In: Etiology of Dementia of Alzheimer’s Type. Henderson AS, Henderson JH, eds. Chichester: John Wiley and Sons, pp. 214–228Google Scholar
  14. Perry EK, Perry RH, Smith CJ, Dick DJ, Fairbairn A, Blessed G, Candy JM, Johnson M, Edwardson JA (1987): Nicotinic receptor abnormalities in Alzheimer’s and Parkinson’s diseases. J Neurol Neurosurg Psychiat 50: pp. 805–809CrossRefGoogle Scholar
  15. Perry RH, Irving D, Blessed G, Fairbairn AF, Perry EK (1990a): Senile dementia of Lewy body type: a clinically and histopathologically distinct form of Lewy body dementia in the elderly. J Neurol Sci 95:119–139CrossRefGoogle Scholar
  16. Perry RH, Irving D, Tomlinson BE (1990b): Lewy body prevalence in the elderly: relationship to psychiatric status, Alzheimer pathology and catecholamine neuronal density. J Neurol Sci 100:223–233CrossRefGoogle Scholar
  17. Smith CJ, Perry EK, Perry RH, Candy JM, Johnson M, Bonham JR, Dick DJ, Fairbairn A, Blessed G, Birdsal NJM (1988): Muscarinic cholinergic receptor subtypes in hippocampus in human cognitive disorders. J Neurochem 50:847–856CrossRefGoogle Scholar
  18. Storandt M (1988): Relationship of normal aging and dementing diseases in later life. In: Etiology of Dementia of Alzheimer’s Type. Henderson AS, Henderson JH, eds. Chichester: John Wiley and Sons, pp. 231–239Google Scholar
  19. Wagner J, Vitali P, Palfreyman MG, Zraika M, Huot S (1982): Simultaneous determination of 3,4-dihydroxyphenylalanine, 5-hydroxytryptophan, dopamine, 4-hydroxy-3-methoxyphenylalanine, norepinephrine, 3,4-dehydroxyphenylacetic acid, homovanillic acid, serotonin and 3,4-dehydroxyindoacetic acid in rat cerebrospinal fluid and brain by high performance liquid chromatography with electrochemical detection. J Neurochem 38:1241–1254CrossRefGoogle Scholar
  20. Yates M, Leake A, Candy JM, Fairbairn AF, McKeith, IG, and Ferrier IN (1990): 5HT2 receptor changes in major depression. Biol Psychiat 27:489–496CrossRefGoogle Scholar

Copyright information

© Birkhäuser Boston 1992

Authors and Affiliations

  • Elaine K. Perry
  • Elizabeth Marshall
  • Anthony Cheng
  • James A. Edwardson
  • Robert H. Perry

There are no affiliations available

Personalised recommendations