α-Synuclein pathology is highly dependent on the case selection

Lewy bodies and dystrophic neurites have been considered a common substrate for dementia, but they are also frequently found in the normal elderly population. The primary component of this pathology involves alpha -synuclein. The main objective of the present study was to estimate the prevalence of alpha -synuclein pathology in aged population, and to assess its relative significance in relation to dementia. The study also investigated whether differences could be detected in alpha -synuclein pathology in relation to age, gender or concomitant Alzheimer's pathology. Furthermore, the influence of sampling strategies was analysed. alpha -Synuclein pathology was assessed using immunohistochemistry in well-characterized post-mortem material. The investigation included patients from a longitudinal study of dementia of Alzheimer's type (n=103, 85% demented), subjects from a prospective longitudinal clinical study of ageing (n=69, 29% demented), a cohort of consecutive clinical post-mortem cases collected for I year (n=262. 12% demented), a sample of forensic post-mortem cases collected for 6 months (n=121, 15%0 demented) and a sample of Brain Bank material (n=234, 26% demented). Overall, alpha -synuclein pathology was found in 14% of all 774 subjects over 40 years of age, and this percentage varied from 8% to 27% according to sampling strategies. These results indicate that the prevalence of alpha -synuclein pathology clearly depends on the selection of material. Furthermore alpha -synuclein pathology was found in 23% of clinically demented patients and in 11% of non-demented subjects. The load of alpha -synuclein pathology was significantly greater in the demented patients versus non-demented subjects indicating that alpha -synuclein pathology is indeed of importance in the pathogenesis of dementia.