To investigate whether cytoplasmic accumulation of BRCA1 occurs in other primary tauopathies.

We immunohistochemistry examined the expression levels and distribution patterns of BRCA1 and other DDR protein, p53-Binding Protein 1 (53BP1), in AD, Pick’s disease (PiD), progressive supranuclear palsy, corticobasal degeneration, and frontotemporal dementia with parkinsonism linked to chromosome 17, and in control without neurological disorders.

In the control subjects, BRCA1 and phosphorylated BRCA1 (pBRCA1) (Ser1524) immunoreactivity were not observed in neurons or glial cells and that for pBRCA1 (Ser1423) and 53BP1 were slightly seen in neuronal nuclei. Both BRCA1 and pBRCA1 (Ser1423) immunoreactivity was elevated and localized within phosphorylated tau inclusions in all tauopathies, whereas pBRCA1 (Ser1524) was mainly associated with Pick bodies in PiD and to a lesser extent with NFTs in AD. On the other hand, 53BP1-immunoreactive deposit tended to be increased in the nucleus of neurons in AD and PSP compared to control cases, but there was no difference in the subcellular localization.

Our present results suggest that DDR dysfunction due to cytoplasmic sequestration of BRCA1 could play a significant role in the pathogenesis of AD and tauopathies.