Spatial Distribution of Tau and β-Amyloid Pathologies and Their Role in Different Alzheimer Disease Phenotypes.

Abstract

Accumulations of β-amyloid (Aβ) and tau are the defining pathologies of Alzheimer disease (AD). Application of PET to AD has enabled us to visualize Aβ and tau pathologies in vivo. In contrast to measuring Aβ and tau in CSF, which is more common in some memory clinics, PET provides information on the spatial distribution of the pathologies. By examining this distribution, Aβ-PET and tau-PET have advanced our understanding of how the disease develops over decades: it starts with the neocortical accumulation of Aβ, which appears to facilitate the spread of tau deposition, followed by cognitive symptoms. Biomarkers of Aβ and tau have also been implemented in the diagnostic framework of AD.1 In clinical practice, Aβ-PET has been used to diagnose AD, and such may soon be the case for tau-PET because results are emerging that tau-PET has promise in differentiating AD from its mimics.2,3 Aβ and tau biomarkers can improve the diagnostic accuracy of the typical amnestic AD, which presents with gradual deterioration of memory and later involves dysfunction in other cognitive domains. They can also identify more challenging AD cases: those with cognitive symptoms less typical of AD. These include phenotypes such as predominant impairment of verbal performance (logopenic AD) or visuospatial performance (posterior cortical atrophy [PCA]). Such cases would previously be identified as probable AD at a very late disease stage or only after a neuropathologic assessment.