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80/100

✓ Peer-reviewed alzhub usefulness score 80 out of 100. Inflammation and the immune system

Topic: Amyloid, tau and blood-test diagnosis

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 -5 ), 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.

Cite this study APA, Vancouver, BibTeX · download .bib or .ris

APA 7th

Bouzid, H., Belk, J. A., Jan, M., Qi, Y., Sarnowski, C., Wirth, S., et al. (2023). Clonal hematopoiesis is associated with protection from Alzheimer's disease. Nature medicine. https://doi.org/10.1038/s41591-023-02397-2

Vancouver

Bouzid H, Belk JA, Jan M, Qi Y, Sarnowski C, Wirth S, et al. Clonal hematopoiesis is associated with protection from Alzheimer's disease. Nature medicine. 2023. doi:10.1038/s41591-023-02397-2. PMID: 37322115.

BibTeX

@article{bouzid2023-37322115,
  author  = {Bouzid, H. and Belk, J. A. and Jan, M. and Qi, Y. and Sarnowski, C. and Wirth, S. and Ma, L. and Chrostek, M. R. and others},
  title   = {{Clonal hematopoiesis is associated with protection from Alzheimer's disease}},
  journal = {Nature medicine},
  year    = {2023},
  doi     = {10.1038/s41591-023-02397-2},
  pmid    = {37322115},
  url     = {https://doi.org/10.1038/s41591-023-02397-2}
}

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Key findings

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.
Individuals with CHIP had a lower risk of AD dementia (meta-analysis odds ratio (OR) = 0.64, P = 3.8 × 10 -5 ), 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.

Why it matters

Using blood DNA from 1,362 people with Alzheimer's and 4,368 without, researchers found that clonal hematopoiesis (CHIP), an expansion of mutated blood stem cells, was linked to a lower risk of Alzheimer's dementia (odds ratio 0.64). The same mutations turned up in a microglia-rich fraction of the brain in seven of eight carriers, and genetic analyses supported a possible causal link. The authors say further studies are needed but suggest CHIP may help lower Alzheimer's risk.

Study details

Study designmeta-analysis
Participants1,362
Evidence strengthHigh

How this study scored 80/100

Published in a top-tier journal, and it is a meta-analysis pooling many studies. Scored zero for effect reported because the record does not state it.

Component	Points	Why
Journal tier	10 / 10	Tier 1 — top-tier general journal (Nature medicine)
Journal's citation record	4 / 4	Nature Medicine: journal h-index 763 (OpenAlex, 2026-10-29)
Study design	12 / 12	A meta-analysis pooling many studies
Strength of evidence	5 / 5	Rated “high” in our summary
Peer-review validation	10 / 10	Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent	3 / 5	2023 — within 6 year(s) of the newest study here
Sample size	3 / 4	1,362 participants
Effect reported	0 / 3	No effect size reported — scores zero (not stated in the record — scored 0)
Studied in people	3 / 3	Studied in people (participant count stated)
Randomized / blinded	0 / 2	A review of other studies — randomization is not credited here
Times cited	5 / 7	Cited 168 times (OpenAlex, 2026-10-10)
Citations per year	4 / 5	33.6 citations a year over 5 year(s) since 2023
Impact for its field and year	5 / 6	Cited 23.7× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	1 / 6	Cited by 2 other studies in this library
Still being cited	3 / 4	Cited 143 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	2 / 4	Last-listed author Siddhartha Jaiswal: h-index 43 (OpenAlex, whole career)
Institution's track record	3 / 3	University of Washington: institution h-index 3,540 (OpenAlex)
Multicenter collaboration	3 / 3	OpenAlex lists 16 institution(s) in 2 countries
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 37322115)
Free to read	2 / 2	Free to read
Total	80 / 100	—

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