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Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1998 May;64(5):653–656. doi: 10.1136/jnnp.64.5.653

Frontal cortical synaptophysin in Lewy body diseases: relation to Alzheimer's disease and dementia

L Hansen 1, S Daniel 1, G Wilcock 1, S Love 1
PMCID: PMC2170082  PMID: 9598683

Abstract

OBJECTIVES—Dementia in Alzheimer's disease correlates closely with loss of neocortical synapses. Similar synaptic loss has been shown in patients whose Alzheimer's disease is also associated with neocortical and brain stem Lewy bodies. The aim was to determine if dementia in Lewy body disease was associated with diminished concentrations of midfrontal cortex synaptophysin.
METHODS—An immunobinding assay was used to measure synaptophysin in postmortem samples of midfrontal cortex from 89 patients with Alzheimer's disease (ages 59-100, mean 79), 22 with combined Lewy body disease and Alzheimer's disease (ages 69-103, mean 79), 15demented patients with "pure" Lewy body disease (ages 57-80, mean 74), nine with neocortical and brain stem Lewy bodies who had Parkinson's disease but were not demented (ages 68-85, mean 79), and 20 neurologically normal controls (ages 58-89, mean 75). The diagnosis was confirmed in all cases by detailed neuropathological examination of the contralateral hemibrain. Seven of the patients in the pure Lewy body disease with dementia group had initially presented with parkinsonism and eight with dementia.
RESULTS—Synaptophysin concentrations (arbitrary units (AU)/µg) in patients with Alzheimer's disease (mean 79 (SD 28)) or combined Lewy body disease and Alzheimer's disease (mean 83 (SD 33)) were significantly lower than in controls (mean 115 (SD 29)) (p=0.002). Synaptophysin concentrations in demented patients with pure Lewy body disease (mean 106 SD 39) and patients with Lewy body disease who were not demented (mean 101 (SD 18)) did not differ significantly from control values or from each other.
CONCLUSION—Loss of midfrontal cortex synapses probably contributes to dementia in Lewy body disease when Alzheimer's disease is also present but not to the dementia of pure Lewy body disease.



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Selected References

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  1. Alford M. F., Masliah E., Hansen L. A., Terry R. D. A simple dot-immunobinding assay for quantification of synaptophysin-like immunoreactivity in human brain. J Histochem Cytochem. 1994 Feb;42(2):283–287. doi: 10.1177/42.2.8288869. [DOI] [PubMed] [Google Scholar]
  2. Bancher C., Braak H., Fischer P., Jellinger K. A. Neuropathological staging of Alzheimer lesions and intellectual status in Alzheimer's and Parkinson's disease patients. Neurosci Lett. 1993 Nov 12;162(1-2):179–182. doi: 10.1016/0304-3940(93)90590-h. [DOI] [PubMed] [Google Scholar]
  3. Bodhireddy S., Dickson D. W., Mattiace L., Weidenheim K. M. A case of Down's syndrome with diffuse Lewy body disease and Alzheimer's disease. Neurology. 1994 Jan;44(1):159–161. doi: 10.1212/wnl.44.1.159. [DOI] [PubMed] [Google Scholar]
  4. Braak H., Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239–259. doi: 10.1007/BF00308809. [DOI] [PubMed] [Google Scholar]
  5. Galasko D., Saitoh T., Xia Y., Thal L. J., Katzman R., Hill L. R., Hansen L. The apolipoprotein E allele epsilon 4 is overrepresented in patients with the Lewy body variant of Alzheimer's disease. Neurology. 1994 Oct;44(10):1950–1951. doi: 10.1212/wnl.44.10.1950. [DOI] [PubMed] [Google Scholar]
  6. Gearing M., Schneider J. A., Rebeck G. W., Hyman B. T., Mirra S. S. Alzheimer's disease with and without coexisting Parkinson's disease changes: apolipoprotein E genotype and neuropathologic correlates. Neurology. 1995 Nov;45(11):1985–1990. doi: 10.1212/wnl.45.11.1985. [DOI] [PubMed] [Google Scholar]
  7. Hansen L. A., Samuel W. Criteria for Alzheimer's disease and the nosology of dementia with Lewy bodies. Neurology. 1997 Jan;48(1):126–132. doi: 10.1212/wnl.48.1.126. [DOI] [PubMed] [Google Scholar]
  8. Hansen L., Salmon D., Galasko D., Masliah E., Katzman R., DeTeresa R., Thal L., Pay M. M., Hofstetter R., Klauber M. The Lewy body variant of Alzheimer's disease: a clinical and pathologic entity. Neurology. 1990 Jan;40(1):1–8. doi: 10.1212/wnl.40.1.1. [DOI] [PubMed] [Google Scholar]
  9. Hughes A. J., Daniel S. E., Blankson S., Lees A. J. A clinicopathologic study of 100 cases of Parkinson's disease. Arch Neurol. 1993 Feb;50(2):140–148. doi: 10.1001/archneur.1993.00540020018011. [DOI] [PubMed] [Google Scholar]
  10. Khachaturian Z. S. Diagnosis of Alzheimer's disease. Arch Neurol. 1985 Nov;42(11):1097–1105. doi: 10.1001/archneur.1985.04060100083029. [DOI] [PubMed] [Google Scholar]
  11. Lantos P. L., Ovenstone I. M., Johnson J., Clelland C. A., Roques P., Rossor M. N. Lewy bodies in the brain of two members of a family with the 717 (Val to Ile) mutation of the amyloid precursor protein gene. Neurosci Lett. 1994 May 19;172(1-2):77–79. doi: 10.1016/0304-3940(94)90666-1. [DOI] [PubMed] [Google Scholar]
  12. Lennox G., Lowe J., Landon M., Byrne E. J., Mayer R. J., Godwin-Austen R. B. Diffuse Lewy body disease: correlative neuropathology using anti-ubiquitin immunocytochemistry. J Neurol Neurosurg Psychiatry. 1989 Nov;52(11):1236–1247. doi: 10.1136/jnnp.52.11.1236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. McKeith I. G., Galasko D., Kosaka K., Perry E. K., Dickson D. W., Hansen L. A., Salmon D. P., Lowe J., Mirra S. S., Byrne E. J. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology. 1996 Nov;47(5):1113–1124. doi: 10.1212/wnl.47.5.1113. [DOI] [PubMed] [Google Scholar]
  14. Mirra S. S., Hart M. N., Terry R. D. Making the diagnosis of Alzheimer's disease. A primer for practicing pathologists. Arch Pathol Lab Med. 1993 Feb;117(2):132–144. [PubMed] [Google Scholar]
  15. Nalbantoglu J., Gilfix B. M., Bertrand P., Robitaille Y., Gauthier S., Rosenblatt D. S., Poirier J. Predictive value of apolipoprotein E genotyping in Alzheimer's disease: results of an autopsy series and an analysis of several combined studies. Ann Neurol. 1994 Dec;36(6):889–895. doi: 10.1002/ana.410360614. [DOI] [PubMed] [Google Scholar]
  16. Perry E. K., Curtis M., Dick D. J., Candy J. M., Atack J. R., Bloxham C. A., Blessed G., Fairbairn A., Tomlinson B. E., Perry R. H. Cholinergic correlates of cognitive impairment in Parkinson's disease: comparisons with Alzheimer's disease. J Neurol Neurosurg Psychiatry. 1985 May;48(5):413–421. doi: 10.1136/jnnp.48.5.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Perry E. K., Marshall E., Perry R. H., Irving D., Smith C. J., Blessed G., Fairbairn A. F. Cholinergic and dopaminergic activities in senile dementia of Lewy body type. Alzheimer Dis Assoc Disord. 1990 Summer;4(2):87–95. [PubMed] [Google Scholar]
  18. Perry E. K., McKeith I., Thompson P., Marshall E., Kerwin J., Jabeen S., Edwardson J. A., Ince P., Blessed G., Irving D. Topography, extent, and clinical relevance of neurochemical deficits in dementia of Lewy body type, Parkinson's disease, and Alzheimer's disease. Ann N Y Acad Sci. 1991;640:197–202. doi: 10.1111/j.1749-6632.1991.tb00217.x. [DOI] [PubMed] [Google Scholar]
  19. Salmon D. P., Galasko D., Hansen L. A., Masliah E., Butters N., Thal L. J., Katzman R. Neuropsychological deficits associated with diffuse Lewy body disease. Brain Cogn. 1996 Jul;31(2):148–165. doi: 10.1006/brcg.1996.0039. [DOI] [PubMed] [Google Scholar]
  20. Samuel W., Galasko D., Masliah E., Hansen L. A. Neocortical lewy body counts correlate with dementia in the Lewy body variant of Alzheimer's disease. J Neuropathol Exp Neurol. 1996 Jan;55(1):44–52. doi: 10.1097/00005072-199601000-00005. [DOI] [PubMed] [Google Scholar]
  21. Scatton B., Rouquier L., Javoy-Agid F., Agid Y. Dopamine deficiency in the cerebral cortex in Parkinson disease. Neurology. 1982 Sep;32(9):1039–1040. doi: 10.1212/wnl.32.9.1039. [DOI] [PubMed] [Google Scholar]
  22. Terry R. D., Masliah E., Salmon D. P., Butters N., DeTeresa R., Hill R., Hansen L. A., Katzman R. Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol. 1991 Oct;30(4):572–580. doi: 10.1002/ana.410300410. [DOI] [PubMed] [Google Scholar]
  23. Weiner M. F., Risser R. C., Cullum C. M., Honig L., White C., 3rd, Speciale S., Rosenberg R. N. Alzheimer's disease and its Lewy body variant: a clinical analysis of postmortem verified cases. Am J Psychiatry. 1996 Oct;153(10):1269–1273. doi: 10.1176/ajp.153.10.1269. [DOI] [PubMed] [Google Scholar]

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