Human brain microglia responses to amyloid beta and tau pathology in high pathology controls and across disease stages
Our data suggest that in normal aging, synaptic Aβ accumulation leads to a diminishing of synaptic CD47 ('don't eat me') signal, accelerating the clearance of malfunctioning Aβ but not p-tau positive synapses. Upregulation of P2ry12 and CD206, accompanied by downregulation of Clec7a, may represent an early and potentially protective response to pre-tangle tau pathology. Later in disease progression, P2ry12 reduction may drive a more reactive, phagocytic phenotype in response to tau pathology, leading to an increase in synaptic CD47 levels and synaptic pathology accumulation.
Authors
- Karen H. Gylys
- Tina Bilousova (ORCID: https://orcid.org/0000-0002-4855-3953)
- Swetha Atluri (ORCID: https://orcid.org/0000-0002-1416-5119)
- Jessica E. Rexach (ORCID: https://orcid.org/0000-0002-4462-7249)
- Mikhail Melnik
- Vivianne Mitri
- Achyutha Kodavatikanti
- Nina Knitowski
Institutions
- University of California, Los Angeles (US)
- University of California, San Francisco (US)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2024-12-01
- DOI
- https://doi.org/10.1002/alz.088080
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Achievement Rewards for College Scientists Foundation
- National Institutes of Health
- Center for AIDS Research, University of Washington
- University of California, Irvine
- National Institute on Aging
- Jonsson Comprehensive Cancer Center
- David Geffen School of Medicine, University of California, Los Angeles
- UCLA AIDS Institute