The process of AD is suggested to start 20 to 30 years before the clinical symptoms appear, with lowering levels of CSF Aβ42 as the first manifestation, whereas increased levels of tau occur later.44 Our findings suggest a negative effect of longer exposure to endogenous estrogen on CSF biomarkers for AD in the preclinical phase of AD. The gene discussed is MAPT; the disease is Alzheimer disease.