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Clonal hematopoiesis is associated with protection from Alzheimer's disease.
Thursday,2023-07-20 14:34 America/Los_Angeles — ecterry
| Title | Clonal hematopoiesis is associated with protection from Alzheimer's disease. |
| Publication Type | Journal Article |
| Year of Publication | 2023 |
| Authors | Bouzid, H, Belk, JA, Jan, M, Qi, Y, Sarnowski, C, Wirth, S, Ma, L, Chrostek, MR, Ahmad, H, Nachun, D, Yao, W, Beiser, A, Bick, AG, Bis, JC, Fornage, M, Longstreth, WT, Lopez, OL, Natarajan, P, Psaty, BM, Satizabal, CL, Weinstock, J, Larson, EB, Crane, PK, C Keene, D, Seshadri, S, Satpathy, AT, Montine, TJ, Jaiswal, S |
| Corporate/Institutional Authors | NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium |
| Journal | Nat Med |
| Volume | 29 |
| Issue | 7 |
| Pagination | 1662-1670 |
| Date Published | 2023 Jul |
| ISSN | 1546-170X |
| Abstract | <p>Clonal hematopoiesis of indeterminate potential (CHIP) is a premalignant expansion of mutated hematopoietic stem cells. As CHIP-associated mutations are known to alter the development and function of myeloid cells, we hypothesized that CHIP may also be associated with the risk of Alzheimer's disease (AD), a disease in which brain-resident myeloid cells are thought to have a major role. To perform association tests between CHIP and AD dementia, we analyzed blood DNA sequencing data from 1,362 individuals with AD and 4,368 individuals without AD. Individuals with CHIP had a lower risk of AD dementia (meta-analysis odds ratio (OR) = 0.64, P = 3.8 × 10), and Mendelian randomization analyses supported a potential causal association. We observed that the same mutations found in blood were also detected in microglia-enriched fraction of the brain in seven of eight CHIP carriers. Single-nucleus chromatin accessibility profiling of brain-derived nuclei in six CHIP carriers revealed that the mutated cells comprised a large proportion of the microglial pool in the samples examined. While additional studies are required to validate the mechanistic findings, these results suggest that CHIP may have a role in attenuating the risk of AD.</p> |
| DOI | 10.1038/s41591-023-02397-2 |
| Alternate Journal | Nat Med |
| PubMed ID | 37322115 |
| PubMed Central ID | PMC10353941 |
| Grant List | DP2 HL157540 / HL / NHLBI NIH HHS / United States DP5 OD029586 / CD / ODCDC CDC HHS / United States R00 AG066849 / AG / NIA NIH HHS / United States |
ePub date:
23/06