Abeta deposition is associated with enhanced cortical alpha-synuclein lesions in Lewy body diseases

Neurobiol Aging. Aug-Sep 2005;26(8):1183-92. doi: 10.1016/j.neurobiolaging.2004.10.006. Epub 2004 Dec 28.

Abstract

In order to understand better the neuropathological substrate of dementia in Parkinson's disease (PD) and to examine its interactions with Alzheimer's disease (AD), we examined autopsy brains from 21 cases of PD and Lewy body disease (LBD) with dementia. We separated brains in two groups according to the presence of Abeta deposits. In brains without Abeta, we found few or no Lewy bodies (LB) in the cerebral cortex. By contrast, in brains with Abeta, we observed significant increases in LB in the cerebral cortex (p < 0.01) and alpha-synuclein immunoreactive lesions in the cingulate cortex (p < 0.01). Immunoblots of alpha-synuclein from cingulate cortex in brains with Abeta showed significantly higher levels of insoluble alpha-synuclein compared to brains without Abeta. Our observations indicate that in cases of PD with dementia, the neocortex is not necessarily involved by LB. Furthermore, the presence of Abeta deposits in the cerebral cortex was associated with extensive alpha-synuclein lesions and higher levels of insoluble alpha-synuclein. This suggests that Abeta enhances the development of cortical alpha-synuclein lesions in cases of PD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / pathology
  • Cerebral Cortex / physiopathology
  • Diagnosis, Differential
  • Female
  • Formates / chemistry
  • Humans
  • Immunohistochemistry / methods
  • Lewy Bodies / metabolism
  • Lewy Bodies / pathology
  • Lewy Body Disease / metabolism*
  • Lewy Body Disease / pathology
  • Lewy Body Disease / physiopathology
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / metabolism*
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Parkinson Disease / physiopathology
  • Plaque, Amyloid / metabolism*
  • Plaque, Amyloid / pathology
  • Synucleins
  • alpha-Synuclein
  • tau Proteins / metabolism

Substances

  • Formates
  • Nerve Tissue Proteins
  • SNCA protein, human
  • Synucleins
  • alpha-Synuclein
  • tau Proteins
  • formic acid