TY - JOUR
T1 - Alterations in Alzheimer's disease microglia transcriptome might be involved in bone pathophysiology
AU - Gharpure, Mohini
AU - Vyavahare, Sagar
AU - Ahluwalia, Pankaj
AU - Gupta, Sonu Kumar
AU - Lee, Tae Jin
AU - Lohakare, Jayant
AU - Kolhe, Ravindra
AU - Lei, Yun
AU - Deak, Ferenc
AU - Lu, Xin Yun
AU - Isales, Carlos M.
AU - Fulzele, Sadanand
N1 - Publisher Copyright:
© 2024
PY - 2024/2
Y1 - 2024/2
N2 - Aging is a major risk factor for multiple chronic disorders in the elderly population, including Alzheimer's disease (AD) and Osteoporosis. AD is a progressive neurodegenerative disease characterized by memory loss. In addition to dementia, several studies have shown that AD patients experience an increased rate of musculoskeletal co-morbidities, such as osteoporosis. Since tissue-specific macrophages contribute to both diseases, this study analyzed the microglia transcriptome of AD mice to determine a common gene signature involved in osteoclast biology. After comparing differentially regulated genes from GEO data sets (GSE93824 and GSE212277), there were 35 common upregulated genes and 89 common downregulated genes. Of these common genes, seven genes are known to play an important role in bone homeostasis. CSF1, SPP1, FAM20C, and Cst7 were upregulated and are associated with osteoclastogenesis and inflammation. Among the downregulated genes, LILRA6, MMP9, and COL18A1 are involved in bone formation and osteoclast regulation. We further validated some of these genes (CSF1, Cst7, and SPP1) in the cortex and the bone of AD mice models. The dysregulation of these microglial genes in AD might provide insights into the co-occurrence of AD and osteoporosis and offer potential therapeutic targets to combat disease progression.
AB - Aging is a major risk factor for multiple chronic disorders in the elderly population, including Alzheimer's disease (AD) and Osteoporosis. AD is a progressive neurodegenerative disease characterized by memory loss. In addition to dementia, several studies have shown that AD patients experience an increased rate of musculoskeletal co-morbidities, such as osteoporosis. Since tissue-specific macrophages contribute to both diseases, this study analyzed the microglia transcriptome of AD mice to determine a common gene signature involved in osteoclast biology. After comparing differentially regulated genes from GEO data sets (GSE93824 and GSE212277), there were 35 common upregulated genes and 89 common downregulated genes. Of these common genes, seven genes are known to play an important role in bone homeostasis. CSF1, SPP1, FAM20C, and Cst7 were upregulated and are associated with osteoclastogenesis and inflammation. Among the downregulated genes, LILRA6, MMP9, and COL18A1 are involved in bone formation and osteoclast regulation. We further validated some of these genes (CSF1, Cst7, and SPP1) in the cortex and the bone of AD mice models. The dysregulation of these microglial genes in AD might provide insights into the co-occurrence of AD and osteoporosis and offer potential therapeutic targets to combat disease progression.
KW - Alzheimer's disease
KW - Bone pathophysiology
KW - Microglia
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UR - http://www.scopus.com/inward/citedby.url?scp=85182014830&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2024.106404
DO - 10.1016/j.nbd.2024.106404
M3 - Article
C2 - 38184014
SN - 0969-9961
VL - 191
JO - Neurobiology of Disease
JF - Neurobiology of Disease
M1 - 106404
ER -