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Microvascular and Cellular Dysfunctions in Alzheimer's Disease: an Integrative Analysis Perspective

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Journal Sci Rep
Specialty Science
Date 2024 Sep 9
PMID 39251797
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Abstract

Alzheimer's disease (AD) is the most common cause of dementia, characterized by memory loss, cognitive decline, personality changes, and various neurological symptoms. The role of blood-brain barrier (BBB) injury, extracellular matrix (ECM) abnormalities, and oligodendrocytes (ODCs) dysfunction in AD has gained increasing attention, yet the detailed pathogenesis remains elusive. This study integrates single-cell sequencing of AD patients' cerebrovascular system with a genome-wide association analysis. It aims to elucidate the associations and potential mechanisms behind pericytes injury, ECM disorder, and ODCs dysfunction in AD pathogenesis. Finally, we identified that abnormalities in the pericyte PI3K-AKT-FOXO signaling pathway may be involved in the pathogenic process of AD. This comprehensive approach sheds new light on the complex etiology of AD and opens avenues for advanced research into its pathogenesis and therapeutic strategies.

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References
1.
Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chetelat G, Teunissen C . Alzheimer's disease. Lancet. 2021; 397(10284):1577-1590. PMC: 8354300. DOI: 10.1016/S0140-6736(20)32205-4. View

2.
Hardy J, Selkoe D . The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science. 2002; 297(5580):353-6. DOI: 10.1126/science.1072994. View

3.
Maccioni R, Farias G, Morales I, Navarrete L . The revitalized tau hypothesis on Alzheimer's disease. Arch Med Res. 2010; 41(3):226-31. DOI: 10.1016/j.arcmed.2010.03.007. View

4.
Terry Jr A, Buccafusco J . The cholinergic hypothesis of age and Alzheimer's disease-related cognitive deficits: recent challenges and their implications for novel drug development. J Pharmacol Exp Ther. 2003; 306(3):821-7. DOI: 10.1124/jpet.102.041616. View

5.
Sweeney M, Sagare A, Zlokovic B . Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat Rev Neurol. 2018; 14(3):133-150. PMC: 5829048. DOI: 10.1038/nrneurol.2017.188. View