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Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1986 Mar;49(3):229–237. doi: 10.1136/jnnp.49.3.229

Alzheimer's disease: a correlative study.

D Neary, J S Snowden, D M Mann, D M Bowen, N R Sims, B Northen, P O Yates, A N Davison
PMCID: PMC1028720  PMID: 2420941

Abstract

In a study of 17 patients with histologically proven Alzheimer's disease the relationship between psychological, pathological and chemical measures of disorder was examined. Severity of dementia, determined by mental test performance, correlated highly with pathological change in large cortical neurons (cell loss and reduction in nuclear and nucleolar volume and cytoplasmic RNA content), to a lesser extent with cortical senile plaque and neurofibrillary tangle frequency and reduction in acetylcholine (ACh) synthesis, and not with reduction in choline acetyltransferase (CAT) activity. A strongly significant relationship was demonstrated between cell loss and reductions in nuclear and nucleolar volume and cytoplasmic RNA content. Reduction in CAT activity and senile plaque frequency were significantly correlated, thereby linking changes in the sub-cortical projection system of the nucleus basalis with the cortical pathology. The pattern of correlations suggests that the dementia of Alzheimer's disease is largely a reflection of the state of large cortical neurons, and it is argued that abnormalities in the latter may not be directly related to primary loss of cholinergic neurons in the subcortex.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blessed G., Tomlinson B. E., Roth M. The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry. 1968 Jul;114(512):797–811. doi: 10.1192/bjp.114.512.797. [DOI] [PubMed] [Google Scholar]
  2. Bowen D. M., Allen S. J., Benton J. S., Goodhardt M. J., Haan E. A., Palmer A. M., Sims N. R., Smith C. C., Spillane J. A., Esiri M. M. Biochemical assessment of serotonergic and cholinergic dysfunction and cerebral atrophy in Alzheimer's disease. J Neurochem. 1983 Jul;41(1):266–272. doi: 10.1111/j.1471-4159.1983.tb11838.x. [DOI] [PubMed] [Google Scholar]
  3. Bowen D. M., Benton J. S., Spillane J. A., Smith C. C., Allen S. J. Choline acetyltransferase activity and histopathology of frontal neocortex from biopsies of demented patients. J Neurol Sci. 1982 Dec;57(2-3):191–202. doi: 10.1016/0022-510x(82)90026-0. [DOI] [PubMed] [Google Scholar]
  4. Bowen D. M., Smith C. B., White P., Davison A. N. Neurotransmitter-related enzymes and indices of hypoxia in senile dementia and other abiotrophies. Brain. 1976 Sep;99(3):459–496. doi: 10.1093/brain/99.3.459. [DOI] [PubMed] [Google Scholar]
  5. DE RENZI E., VIGNOLO L. A. The token test: A sensitive test to detect receptive disturbances in aphasics. Brain. 1962 Dec;85:665–678. doi: 10.1093/brain/85.4.665. [DOI] [PubMed] [Google Scholar]
  6. Mann D. M., Neary D., Yates P. O., Lincoln J., Snowden J. S., Stanworth P. Alterations in protein synthetic capability of nerve cells in Alzheimer's disease. J Neurol Neurosurg Psychiatry. 1981 Feb;44(2):97–102. doi: 10.1136/jnnp.44.2.97. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Mann D. M., Yates P. O., Marcyniuk B. Alzheimer's presenile dementia, senile dementia of Alzheimer type and Down's syndrome in middle age form an age related continuum of pathological changes. Neuropathol Appl Neurobiol. 1984 May-Jun;10(3):185–207. doi: 10.1111/j.1365-2990.1984.tb00351.x. [DOI] [PubMed] [Google Scholar]
  8. Morimatsu M., Hirai S., Muramatsu A., Yoshikawa M. Senile degenerative brain lesions and dementia. J Am Geriatr Soc. 1975 Sep;23(9):390–406. doi: 10.1111/j.1532-5415.1975.tb00425.x. [DOI] [PubMed] [Google Scholar]
  9. Mountjoy C. Q., Rossor M. N., Iversen L. L., Roth M. Correlation of cortical cholinergic and GABA deficits with quantitative neuropathological findings in senile dementia. Brain. 1984 Jun;107(Pt 2):507–518. doi: 10.1093/brain/107.2.507. [DOI] [PubMed] [Google Scholar]
  10. Mountjoy C. Q., Roth M., Evans N. J., Evans H. M. Cortical neuronal counts in normal elderly controls and demented patients. Neurobiol Aging. 1983 Spring;4(1):1–11. doi: 10.1016/0197-4580(83)90048-9. [DOI] [PubMed] [Google Scholar]
  11. Neary D., Snowden J. S., Bowen D. M., Sims N. R., Mann D. M., Benton J. S., Northen B., Yates P. O., Davison A. N. Neuropsychological syndromes in presenile dementia due to cerebral atrophy. J Neurol Neurosurg Psychiatry. 1986 Feb;49(2):163–174. doi: 10.1136/jnnp.49.2.163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Nelson H. E., O'Connell A. Dementia: the estimation of premorbid intelligence levels using the New Adult Reading Test. Cortex. 1978 Jun;14(2):234–244. doi: 10.1016/s0010-9452(78)80049-5. [DOI] [PubMed] [Google Scholar]
  13. Pearson R. C., Sofroniew M. V., Cuello A. C., Powell T. P., Eckenstein F., Esiri M. M., Wilcock G. K. Persistence of cholinergic neurons in the basal nucleus in a brain with senile dementia of the Alzheimer's type demonstrated by immunohistochemical staining for choline acetyltransferase. Brain Res. 1983 Dec 19;289(1-2):375–379. doi: 10.1016/0006-8993(83)90046-x. [DOI] [PubMed] [Google Scholar]
  14. Perry E. K., Perry R. H., Blessed G., Tomlinson B. E. Necropsy evidence of central cholinergic deficits in senile dementia. Lancet. 1977 Jan 22;1(8004):189–189. doi: 10.1016/s0140-6736(77)91780-9. [DOI] [PubMed] [Google Scholar]
  15. Perry E. K., Tomlinson B. E., Blessed G., Bergmann K., Gibson P. H., Perry R. H. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J. 1978 Nov 25;2(6150):1457–1459. doi: 10.1136/bmj.2.6150.1457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rossor M. N. Parkinson's disease and Alzheimer's disease as disorders of the isodendritic core. Br Med J (Clin Res Ed) 1981 Dec 12;283(6306):1588–1590. doi: 10.1136/bmj.283.6306.1588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rossor M., Fahrenkrug J., Emson P., Mountjoy C., Iversen L., Roth M. Reduced cortical choline acetyltransferase activity in senile dementia of Alzheimer type is not accompanied by changes in vasoactive intestinal polypeptide. Brain Res. 1980 Nov 10;201(1):249–253. doi: 10.1016/0006-8993(80)90795-7. [DOI] [PubMed] [Google Scholar]
  18. Sims N. R., Bowen D. M., Allen S. J., Smith C. C., Neary D., Thomas D. J., Davison A. N. Presynaptic cholinergic dysfunction in patients with dementia. J Neurochem. 1983 Feb;40(2):503–509. doi: 10.1111/j.1471-4159.1983.tb11311.x. [DOI] [PubMed] [Google Scholar]
  19. Sims N. R., Marek K. L., Bowen D. M., Davison A. N. Production of [14C]acetylcholine and [14C]carbon dioxide from [U-14C]glucose in tissue prisms from aging rat brain. J Neurochem. 1982 Feb;38(2):488–492. doi: 10.1111/j.1471-4159.1982.tb08654.x. [DOI] [PubMed] [Google Scholar]
  20. Whitehouse P. J., Price D. L., Struble R. G., Clark A. W., Coyle J. T., Delon M. R. Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain. Science. 1982 Mar 5;215(4537):1237–1239. doi: 10.1126/science.7058341. [DOI] [PubMed] [Google Scholar]
  21. Wilcock G. K., Esiri M. M., Bowen D. M., Smith C. C. Alzheimer's disease. Correlation of cortical choline acetyltransferase activity with the severity of dementia and histological abnormalities. J Neurol Sci. 1982 Dec;57(2-3):407–417. doi: 10.1016/0022-510x(82)90045-4. [DOI] [PubMed] [Google Scholar]
  22. Wilcock G. K., Esiri M. M. Plaques, tangles and dementia. A quantitative study. J Neurol Sci. 1982 Nov;56(2-3):343–356. doi: 10.1016/0022-510x(82)90155-1. [DOI] [PubMed] [Google Scholar]

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