Abnormal Sp1 Transcription Factor Expression in Alzheimer Disease and Tauopathies

Sp1 transcription factor expression was examined by immunohistochemistry, immunofluorescence and confocal microscopy in Alzheimer disease (AD), Pick disease (PiD), progressive supranuclear palsy (PSP), Parkinson disease (PD) and Dementia with Lewy bodies (DLB). Sp1 partly co-localizes with hyper-phosphorylated tau deposits in neurofibrillary tangles, dystrophic neurites of senile plaques and neuropil threads in AD, and in neurons, astrocytes and oligodendrocytes bearing hyper-phosphorylated tau in PiD and PSP. Sp1 is not found in alpha-synuclein inclusions in PD and DLB. These modifications are not associated with changes in the total expression levels of Sp1, as revealed with gel electrophoresis and Western blotting of brain homogenates. Furthermore, no co-immunoprecipitation of Sp1 and phospho-tau was observed in AD and PiD cases. Since Sp1 binding sites are present in the promoters of several genes involved in amyloid and tau, and Sp1 is regulated by oxidative stress, the present findings suggest that Sp1 deposition in hyper-phosphorylated tau deposits may have functional consequences in the pathology of AD and other tauopathies.