The effects of Alzheimer’s disease genetic risk factors APOE and TREM2 on tau pathology

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by protein aggregation of amyloid-beta fragments in the brain. This is followed by hyperphosphorylation of tau which accumulates to form neurofibrillary tangles (NFTs). Clinical symptoms of AD are related to cognitive decline and memory issues caused by the loss of synapses and the death of neurons. Triggering Receptor Expressed on Myeloid Cells (TREM2) is a transmembrane protein expressed in microglia and is involved in immune responses. Certain genetic variants of TREM2 are significant risk factors for AD. Apolipoprotein E (APOE) is another protein that aids in lipid transport and other metabolic and immunomodulatory functions and its genetic variants also predispose individuals to AD. A great deal of research has been done to understand how TREM2 and APOE variants affect amyloid-beta deposition but only recently has their effects on tau pathology in AD been investigated. This paper aims to provide a guide on how TREM2 and APOE genes affect tau pathology.