TY - JOUR
T1 - Microglial efferocytosis
T2 - Diving into the Alzheimer's disease gene pool
AU - Romero-Molina, Carmen
AU - Garretti, Francesca
AU - Andrews, Shea J.
AU - Marcora, Edoardo
AU - Goate, Alison M.
N1 - Funding Information:
National Institutes of Health (U01AG058635, U01AG032984, P30AG066514), JPB Foundation (A.M.G.), Neurodegeneration Consortium (A.M.G. and E.M.), and BrightFocus Foundation (A2017458S, E.M.). Postdoctoral Fellowship from Fundacion Alfonso Martin Escudero (C.R.-M.). Figures 2, 3 and 4 were created using BioRender.com. C.R.-M. and F.G. wrote the initial manuscript and conceptualized the figures. A.M.G. and E.M. reviewed and edited the manuscript and figures. S.J.A. generated Figure 1 and reviewed the manuscript. All authors approved the final version. A.M.G. is on the scientific advisory boards for Genentech and Muna Therapeutics. A.M.G. is a member of the advisory board for the Cell Press Journal Med. A.M.G. has served as a consultant for AbbVie.
Funding Information:
National Institutes of Health ( U01AG058635 , U01AG032984 , P30AG066514 ), JPB Foundation (A.M.G.), Neurodegeneration Consortium (A.M.G. and E.M.), and BrightFocus Foundation ( A2017458S , E.M.). Postdoctoral Fellowship from Fundacion Alfonso Martin Escudero (C.R.-M.). Figures 2 , 3 and 4 were created using BioRender.com .
Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/11/2
Y1 - 2022/11/2
N2 - Genome-wide association studies and functional genomics studies have linked specific cell types, genes, and pathways to Alzheimer's disease (AD) risk. In particular, AD risk alleles primarily affect the abundance or structure, and thus the activity, of genes expressed in macrophages, strongly implicating microglia (the brain-resident macrophages) in the etiology of AD. These genes converge on pathways (endocytosis/phagocytosis, cholesterol metabolism, and immune response) with critical roles in core macrophage functions such as efferocytosis. Here, we review these pathways, highlighting relevant genes identified in the latest AD genetics and genomics studies, and describe how they may contribute to AD pathogenesis. Investigating the functional impact of AD-associated variants and genes in microglia is essential for elucidating disease risk mechanisms and developing effective therapeutic approaches.
AB - Genome-wide association studies and functional genomics studies have linked specific cell types, genes, and pathways to Alzheimer's disease (AD) risk. In particular, AD risk alleles primarily affect the abundance or structure, and thus the activity, of genes expressed in macrophages, strongly implicating microglia (the brain-resident macrophages) in the etiology of AD. These genes converge on pathways (endocytosis/phagocytosis, cholesterol metabolism, and immune response) with critical roles in core macrophage functions such as efferocytosis. Here, we review these pathways, highlighting relevant genes identified in the latest AD genetics and genomics studies, and describe how they may contribute to AD pathogenesis. Investigating the functional impact of AD-associated variants and genes in microglia is essential for elucidating disease risk mechanisms and developing effective therapeutic approaches.
KW - Alzheimer's disease
KW - cholesterol metabolism
KW - efferocytosis
KW - endolysosomal system
KW - functional genomics
KW - gene expression regulation
KW - human genetics
KW - immunometabolism
KW - innate immune response
KW - microglia
KW - phagocytosis
UR - http://www.scopus.com/inward/record.url?scp=85140808524&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2022.10.015
DO - 10.1016/j.neuron.2022.10.015
M3 - Review article
AN - SCOPUS:85140808524
SN - 0896-6273
VL - 110
SP - 3513
EP - 3533
JO - Neuron
JF - Neuron
IS - 21
ER -