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68/100

✓ Peer-reviewed alzhub usefulness score 68 out of 100. Genetics

Topic: Brain proteins, microglia and lab models

Plain-language summary

Two regions achieved genome-wide significance with TDP-43: apolipoprotein E (APOE) and TMEM106B. Three loci reached genome-wide significance with HS: APOE, TMEM106B, and granulin precursor (GRN). Fine mapping of TMEM106B identified 93 variants in the credible set. Mediation analyses showed that genetic effects on HS were partially mediated through TDP-43 proteinopathy. We identified associations with TDP-43 inclusion and HS, showing shared genetic risk across frontotemporal lobar degeneration, amyotrophic lateral sclerosis, Alzheimer's disease, and limbic-predominant age-related TDP-43 encephalopathy. HIGHLIGHTS: HS and TDP-43 contribute to dementia and often co-occur. The etiology and relationship of HS and TDP-43 remains unclear. HS and TDP-43 share genetic risk factors in the genes APOE and TMEM106B. Genes have direct effects on HS, with additional effects mediated through TDP-43.

What this study adds

Evidence grade: High

This is a pooled review of 9,509 participants. This genetic study found that TDP-43 proteinopathy and hippocampal sclerosis share risk genes, including APOE and TMEM106B, with effects on hippocampal sclerosis partly mediated through TDP-43. It identifies shared genetic risk factors but does not test any treatment, cure, or prevention.

Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.

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

APA 7th

Godrich, D., Pasteris, J., Martin, E. R., Kunkle, B. W., Naj, A. C., Hamilton, K., et al. (2025). Genome‐wide association studies of TDP‐43 proteinopathy and hippocampal sclerosis reveal shared genetic associations with APOE and TMEM106B. Alzheimer s & Dementia. https://doi.org/10.1002/alz.70760

Vancouver

Godrich D, Pasteris J, Martin ER, Kunkle BW, Naj AC, Hamilton K, et al. Genome‐wide association studies of TDP‐43 proteinopathy and hippocampal sclerosis reveal shared genetic associations with APOE and TMEM106B. Alzheimer s & Dementia. 2025. doi:10.1002/alz.70760. PMID: 41208712.

BibTeX

@article{godrich2025-41208712,
  author  = {Godrich, Dana and Pasteris, Jeremy and Martin, Eden R. and Kunkle, Brian W. and Naj, Adam Christian and Hamilton, Kara and Wang, Hui and Lee, Wan‐Ping and others},
  title   = {{Genome‐wide association studies of TDP‐43 proteinopathy and hippocampal sclerosis reveal shared genetic associations with APOE and TMEM106B}},
  journal = {Alzheimer s \& Dementia},
  year    = {2025},
  doi     = {10.1002/alz.70760},
  pmid    = {41208712},
  url     = {https://doi.org/10.1002/alz.70760}
}

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How to read this study

Design: this is a pooled review. It combines earlier studies, so it is only as good as the studies it pools. Check how many were included, whether they were similar enough to combine, and whether the authors report inconsistency between them.
Size: the record lists 9,509 participants. Ask whether that is enough for the question, and who they were.
Effect: the record gives no effect size, so the summary above cannot say how large any difference was.

What the evidence grade means here

This page is graded high. alzhub.org assigns the grade automatically from keywords in the abstract, not from reading the paper. High means the abstract mentions a randomized design, a meta-analysis or a systematic review. It can add at most 5 of the 100 points in the study score, and it is a label about design, not a verdict on whether the findings are true.

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Key findings

Two regions achieved genome-wide significance with TDP-43: apolipoprotein E (APOE) and TMEM106B.
Three loci reached genome-wide significance with HS: APOE, TMEM106B, and granulin precursor (GRN).
Fine mapping of TMEM106B identified 93 variants in the credible set.
Mediation analyses showed that genetic effects on HS were partially mediated through TDP-43 proteinopathy.
We identified associations with TDP-43 inclusion and HS, showing shared genetic risk across frontotemporal lobar degeneration, amyotrophic lateral sclerosis, Alzheimer's disease, and limbic-predominant age-related TDP-43 encephalopathy.

Why it matters

This genetic study found that TDP-43 proteinopathy and hippocampal sclerosis share risk genes, including APOE and TMEM106B, with effects on hippocampal sclerosis partly mediated through TDP-43. It identifies shared genetic risk factors but does not test any treatment, cure, or prevention.

New to this subject? Start with our plain-English guide: Genetics →

Study details

Study designmeta-analysis
Participants9,509
Evidence strengthHigh

How this study scored 68/100

Published in a peer-reviewed 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	7 / 10	Tier 3 — peer-reviewed journal (Alzheimer s & Dementia)
Journal's citation record	2 / 4	Alzheimer s & Dementia: journal h-index 228 (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	4 / 5	2025 — within 3 year(s) of the newest study here
Sample size	3 / 4	9,509 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	2 / 7	Cited 9 times (OpenAlex, 2026-10-10)
Citations per year	2 / 5	3.0 citations a year over 3 year(s) since 2025
Impact for its field and year	3 / 6	Cited 5.1× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	1 / 6	Cited by 1 other studies in this library
Still being cited	1 / 4	Cited 9 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	3 / 4	Last-listed author Gary W. Beecham: h-index 53 (OpenAlex, whole career)
Institution's track record	3 / 3	University of Washington: institution h-index 3,540 (OpenAlex)
Multicenter collaboration	3 / 3	OpenAlex lists 15 institution(s) in 2 countries
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 41208712)
Free to read	2 / 2	Free to read
Total	68 / 100	—

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