A critical appraisal of the link between apolipoprotein E and Tau

The apolipoprotein E ( APOE ) genotype has traditionally been associated with Alzheimer's disease (AD) and, more specifically, with the severity of cerebral β-amyloidosis in the form of Aβ plaques and cerebral amyloid angiopathy (CAA). However, a growing body of research has examined its potential impact on Tau pathology.

Here we critically review the evidence supporting a differential effect of APOE alleles on Tau in the context of AD and non-AD tauopathies, from genetic, neuropathological, and biomarker studies to preclinical studies in mouse models and human inducible pluripotent stem-cells (hiPSCs)-derived brain cells.

Genetic, neuropathological, and preclinical studies in transgenic mice have yielded somewhat conflicting results, whereas most multitracer PET imaging studies on individuals along the normal aging to AD dementia continuum support an Aβ-independent effect of the APOE ε4 allele on the tauopathy of AD. More clinical and preclinical research is needed to elucidate the link between APOE and Tau.