Neurofibrillary tau pathology modulated by genetic variation of α‐synuclein

Abstract

We analyzed whether genetic variation of α‐synuclein modulates the extent of neuropathological changes in a population‐based autopsied sample of 272 elderly Finns. None of the 11 markers was associated with the extent of neocortical β‐amyloid pathology. The intron 4 marker rs2572324 was associated with the extent of neurofibrillary pathology (p = 0.0006, permuted p = 0.004; Braak stages IV‐VI vs 0‐II). The same variant also showed a trend for association with neocortical Lewy‐related pathology. These results suggest for the first time that variation of α‐synuclein modulates neurofibrillary tau pathology and support the recent observations of an interaction of α‐synuclein and tau in neurodegeneration. Ann Neurol 2008