MAPT and Alzheimer disease: As a result of the amyloid cascade hypothesis, efforts to develop therapies for AD have focused mainly on reducing levels of Aβ in the brain,[35] but more than 100 candidate treatment compounds have failed in this attempt.[36, 37] While growing research has indicated that hyperphosphorylated tau and NFTs seem more strongly correlated with cognition in multivariate analyses and synaptic and neuronal loss, which are closely associated with memory deficits.