https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.13020
APOE and immunity: Research highlights
Courtney M. Kloske, et al.
Alzheimer’s & Dementia
First published: 28 March 2023 https://doi.org/10.1002/alz.13020
As you would expect from a review based on a conference, this paper addresses many different topics linked to APOE and the immune system. There are plenty of references for further research if a particular topic interests you.1 INTRODUCTION
The two well-established hallmark pathologies of Alzheimer's disease (AD)—extracellular plaques of aggregated amyloid beta (Aβ) and intraneuronal tangles of hyperphosphorylated, aggregated tau—characterize all cases of AD and have been shown to play a direct role in AD-related neurodegeneration. ... researchers have used genome-wide association studies (GWASs) and whole genome/whole exome sequencing (WGS/WES) studies to identify more than 30 AD-related risk loci.
Among gene variants that are associated with an increased risk for LOAD, more than half are linked to immune cell function. To date, the strongest known genetic risk factor for LOAD is the apolipoprotein E (APOE) ε4 variant, which, during the past decade, has been hypothesized to play a role in AD largely through its immunomodulatory functions.
The triggering receptor expressed on myeloid cells 2 (TREM2), which is expressed by microglia in the central nervous system (CNS), likely plays a significant role in THE immunomodulatory functions of APOE, and genetic studies show that rare TREM2 variants are among important risk factors for AD.
In turn, microglia play a principal role in the neuroinflammation that accompanies the accumulation of Aβ during earlier stages of disease, as well as immune dysregulation that modulates disease progression throughout the course of AD.
Building on a foundation of established and strongly suspected roles of APOE, TREM2, microglia, and immune changes in AD, current research focuses on understanding these roles while identifying new intricately linked biological/pathophysiological mechanisms and pathways, with the goal of determining how the modulation of one or more of these components might be effectively targeted in drug development
