Lewy body-related α-synucleinopathy in aging

Abstract

In order to clarify the significance of Lewy body (LB)-related α-synucleinopathy in aging, we investigated the incidence of LBs in 1241 consecutive autopsy cases (663 male and 578 female) from a community-based general geriatric hospital between 1995 and 2002. LB pathology was evaluated histologically in sections stained with hematoxylin and eosin and immunocytochemically with anti-ubiquitin and anti- α-synuclein antibodies. Cases without LBs were classified into LB Stage 0 (987 cases). Cases with LBs were categorized as follows. LB Stage I: incidental LBs without neuronal degeneration (149 cases); LB Stage II: LB-related neuronal degeneration without documentation of attributable clinical symptoms (47 cases); LB Stage III: Parkinson disease (PD) without dementia (10 cases); LB Stage IV: dementia with Lewy bodies (DLB) and PD with dementia (PDD), presenting with a Lewy score fulfilling the criteria for transitional (limbic) form (25 cases) on the 1996 Consensus Guidelines for DLB; and LB stage V: DLB and PDD, with a Lewy body score fulfilling the criteria for neocortical form (23 cases). The average age at death of cases with LBs was older than that of cases without LBs. The average LB stage increased with age. There were no gender differences in the grade of LB pathology. The G284A polymorphism in the paraoxonase 1 gene was associated with men in LB stage equal to or above II, and suggests a gender-specific risk factor. LB Stage V had higher Braak Stage for neurofibrillary tangle (NFT) and senile plaque (SP) than the background and also had a higher frequency of apolipoprotein E ε4. Cases of higher SP stage with dementia tended to have higher LB stage. Our findings suggest that LBs cause cognitive decline synergistically with Alzheimer-type senile changes, especially with senile plaques. Further study of these correlations should be carried out.