Along with increased phosphorylation and deposition of tau in AD brain, there is also increased ERα being co-purified with PHFs or co-immunoprecipitated by tau-5 antibody in AD brain, demonstrating increased sequestration of ERα by NFTs in the pyramidal neurons in AD brain which likely limits the bioavailability of functional ERα and results in functional consequences. This evidence concerns the gene MAPT and Alzheimer disease.