Year: 2024
Type: article
Abstract: BACKGROUND: Recent evidence suggests both the innate and adaptive immune system are involved in the pathogenesis of Alzheimer's disease. We recently showed that the number of T cells, especially cytotoxic T cells, are increased in areas of tauopathy both in an animal model of tau-mediated neurodegeneration as well as in the AD brain. We also found that depletion of T cells as well as microglia were both strongly neuroprotective in P301S tau transgenic mice (PMID: 36890231). We have been further characterizing T cells in this model as well assessing for other evidence for a role of the adaptive immune system in this model. METHOD: We crossed P301S mice with Rag2KO mice that lack both T and B cells and then analyzed the mice at 9.5 months of age. RESULT: P301S/Rag2KO mice have few to no T cells in the brain but also have strong suppression of the brain's innate immune response and have significantly less brain atrophy and loss of synapses and compared to P301S mice. CONCLUSION: This provides further evidence of a role for the adaptive immune response in tau-mediated neurodegeneration.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.087778
Author: David M. Holtzman
Institution: Washington University in St. Louis
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,000
OpenAlex ID: W4406050767