However, recent evidence shows how approximately 15–20 years before the onset of cognitive deficits, amyloid starts accumulating, followed by microgliosis and neurofibrillary tangle tau pathology [67], making mild to moderate dementia a relatively advanced stage of AD where significant irreversible neuronal and synaptic loss has occurred and therapeutic countermeasures are likely to be less effective [67]. The gene discussed is MAPT; the disease is Alzheimer disease.