Abnormal α-synuclein solubility, aggregation and nitration in the frontal cortex in Pick's disease

Abstract

Abnormal solubility and aggregation of α-synuclein have been observed in the frontal cortex in three cases with Pick's disease (PiD) when compared with age-matched controls. Bands of 45 kDa and higher molecular weight were detected in the SDS-soluble fractions only in PiD. Patterns in PiD differed from that observed in the cerebral cortex in Lewy body diseases which were examined in parallel. Immunoblots to α-synuclein nitrated in tyrosines revealed bands of 45 and 60 kDa in Dxc- and SDS-soluble fractions in the frontal cortex (which is vulnerable to PiD) but not in the occipital cortex (which is resistant to this degenerative disease). Moreover, nitrated α-synuclein was found in Lewy bodies and neurites in synucleinopathies but diffusely in the cytoplasm of scattered neurons in PiD. These findings demonstrate abnormal and distinct α-synuclein solubility and aggregation, and α-synuclein nitration without formation of Lewy bodies in the frontal cortex in PiD.