Year: 2023
Type: review
Abstract: Despite expressing many key risk genes, the role of microglia in late-onset Alzheimer's disease pathophysiology is somewhat ambiguous, with various phenotypes reported to be either harmful or protective. Herein, we review some key findings from clinical and animal model investigations, discussing the role of microglial genetics in mediating perturbations from homeostasis. We note that impairment to protective phenotypes may include prolonged or insufficient microglial activation, resulting in dysregulated metabolomic (notably lipid-related) processes, compounded by age-related inflexibility in dynamic responses. Insufficiencies of mouse genetics and aggressive transgenic modelling imply severe limitations in applying current methodologies for aetiological investigations. Despite the shortcomings, widely used amyloidosis and tauopathy models of the disease have proven invaluable in dissecting microglial functional responses to AD pathophysiology. Some recent advances have brought modelling tools closer to human genetics, increasing the validity of both aetiological and translational endeavours.
Source: Molecular Neurodegeneration
Authors: Ari Sudwarts, Gopal Thinakaran
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,990
Awards: Identifying the interactome and non-autonomous signalling of risk-gene BIN1 in amyloid-responsive microglia, G2941799179, G3083888720, G3735900962, The role of Alzheimer's disease GWAS risk factor BIN1 in tau neuropathology and propagation in vivo, RETIREMENT AND MARITAL QUALITY, G6840747904, G7425301053, The role of elevated BIN1 expression in Alzheimer's disease, Modeling Alzheimer's disease genetic variants in hiPSC, Microglial function of GWAS risk factor BIN1 in Alzheimer's disease pathogenesis and inflammatory signaling, The role of Alzheimer's disease GWAS risk factor BIN1 in tau neuropathology and propagation in vivo, Microglial function of GWAS risk factor BIN1 in Alzheimer's disease pathogenesis and inflammatory signaling
OpenAlex ID: W4388823601