Alpha-synuclein-immunoreactive cortical Lewy bodies are associated with cognitive impairment in Parkinson's disease

Acta Neuropathol. 2000 Sep;100(3):285-90. doi: 10.1007/s004019900168.


Amygdala, hippocampus and six cortical gyri were examined for the Lewy body (LB) degeneration and Alzheimer's disease (AD) type changes in 45 patients with Parkinson's disease (PD). For detection of LBs, the brain areas were stained with an antibody against alpha-synuclein. The extent of neuropathological lesions was investigated in relation to cognitive dysfunction and apolipoprotein E (apoE) epsilon4 allele dosage. At least one cortical LB was found in 95% of cases (43/45). Furthermore, 40% of cases (18/45) had histological findings of definite AD (CERAD class C). Those PD cases with the apoE epsilon4 allele had a significantly greater number of cortical LBs than those without the apoE epsilon4 allele, but this was statistically significant only in precentral, angular and temporal gyri. The LB density correlated better with the number of plaques than with the density of tangles. The number of LBs in several cortical areas correlated significantly with the cognitive impairment. In stepwise linear regression analysis, the number of LBs in the cingulate gyrus and the amount of tangles in the temporal cortex remained statistically significant. When the CERAD class C was excluded, the correlation between cognitive decline and the number of LBs in cortical areas became even more pronounced. A stepwise linear regression analysis in these cases found the number of LBs in the frontal gyrus to be the statistically most significant predictor of cognitive impairment. This study shows, for the first time, that in PD, alpha-synuclein-positive cortical LBs are associated with cognitive impairment independent of AD-type pathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology
  • Amygdala / metabolism
  • Amygdala / pathology
  • Amygdala / physiopathology
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / pathology
  • Cerebral Cortex / physiopathology
  • Cognition Disorders / metabolism*
  • Cognition Disorders / pathology
  • Cognition Disorders / physiopathology
  • Female
  • Humans
  • Lewy Bodies / metabolism*
  • Lewy Bodies / pathology
  • Male
  • Middle Aged
  • Nerve Degeneration / metabolism*
  • Nerve Degeneration / pathology
  • Nerve Tissue Proteins / metabolism*
  • Neurofibrillary Tangles / pathology
  • Neurons / metabolism*
  • Neurons / pathology
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Parkinson Disease / physiopathology
  • Plaque, Amyloid / pathology
  • Synucleins
  • alpha-Synuclein


  • Nerve Tissue Proteins
  • SNCA protein, human
  • Synucleins
  • alpha-Synuclein