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 α‐synuclein. The main objective of the present study was to estimate the prevalence of α‐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 α‐synuclein pathology in relation to age, gender or concomitant Alzheimer's pathology. Furthermore, the influence of sampling strategies was analysed. α‐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 1 year (n = 262, 12% demented), a sample of forensic post‐mortem cases collected for 6 months (n = 121, 15% demented) and a sample of Brain Bank material (n = 234, 26% demented). Overall, α‐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 α‐synuclein pathology clearly depends on the selection of material. Furthermore α‐synuclein pathology was found in 23% of clinically demented patients and in 11% of non‐demented subjects. The load of α‐synuclein pathology was significantly greater in the demented patients versus non‐demented subjects indicating that α‐synuclein pathology is indeed of importance in the pathogenesis of dementia.