MAPT and Alzheimer disease: AβpE has been considered to be a principal initiator of early-stage AD pathogenesis and has been shown to correlate with tau pathology and cognitive decline in AD (10, 12, 15, 19, 49), whereas plasma Aβ42 was found to be inversely correlated with cortical Aβ burden, likely due to impaired Aβ plaque clearance from the brain or sequestration and deposition of Aβ species within the brain.