MAPT and Cognitive impairment: There is a general consensus that biomarkers representing hallmark pathologies in AD, such as extracellular cerebral amyloid deposition and intracellular phosphorylated tau tangle accumulation, precede neurodegeneration biomarkers.3 In clinical AD, these biomarkers have been estimated to deviate approximately 10–15 years before the earliest signs of cognitive impairment,4 with some reports of amyloid changing before tau.