This page is alzhub.org's plain-English summary of a published study, not the paper itself. It is generated from the record we hold for this study, sourced and linked below — check the original for the full text and methods.

59/100

✓ Peer-reviewed alzhub usefulness score 59 out of 100. Genetics

Topic: Brain proteins, microglia and lab models

Importance Transactive response DNA-binding protein 43 (TDP-43) is associated with Alzheimer disease (AD), progressive hippocampal atrophy, and cognitive decline. The apolipoprotein E (APOE) ε4 allele is strongly associated with β-amyloid (Aβ) aggregation and risk of AD, but its association with TDP-43 is unknown. Objective To determine whether the APOE ε4 allele is a risk factor for TDP-43. Design, setting, participants This cross-sectional, genetic-histologic study analyzed APOE genotype, TDP-43 status (positive vs negative), Aβ status (positive vs negative), and tau neurofibrillary tangle stage (B0, Braak stage 0; B1, Braak stages I-II; B2, Braak stages III-IV; B3, Braak stage ≥ V). We fit structural equation models to map the association between APOE and TDP-43, Aβ, and tau, accounting for age and hippocampal sclerosis. We identified 751 participants with an AD pathological spectrum diagnosis and completed Aβ, tau, and TDP-43 data who were enrolled in the Mayo Clinic Alzheimer Disease Research Center, Mayo Clinic Alzheimer Disease Patient Registry, or the population based Mayo Clinic Study of Aging and died between May 12, 1999, and December 31, 2015. However, 13 were excluded from the analyses because of missing APOE data, leaving a total of 738 participants. Main outcomes and measures Transactive response DNA-binding protein 43 was the main outcome of interest. We hypothesized that the APOE ε4 allele would be significantly directly and indirectly associated with TDP-43. Results The 751 study participants were older (median age [interquartile range], 87 years [51-105 years]), 395 (54%) were women, and 324 (44%) were APOE ε4 carriers. The patients died between May 12, 1999, and December 31, 2015. Accounting for age, Aβ, and tau, APOE ε4 had a direct association with TDP-43 (estimate [SE], 0.31 (0.11); P = .01). The association was present among individuals with an intermediate to high likelihood of having AD (neurofibrillary tangle stage B2/B3; n = 604 [81.8%]; estimate [SE], 0.51 [0.11]; P Conclusions and relevance The study's findings, which mapped a system of risk factors and outcomes, showed that the APOE ε4 allele appears to be a risk factor for TDP-43 independently of Aβ in patients with AD.

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

APA 7th

Wennberg, A. M., Tosakulwong, N., Lesnick, T. G., Murray, M. E., Whitwell, J. L., Liesinger, A. M., et al. (2018). Association of Apolipoprotein E ε4 With Transactive Response DNA-Binding Protein 43. JAMA neurology. https://doi.org/10.1001/jamaneurol.2018.3139

Vancouver

Wennberg AM, Tosakulwong N, Lesnick TG, Murray ME, Whitwell JL, Liesinger AM, et al. Association of Apolipoprotein E ε4 With Transactive Response DNA-Binding Protein 43. JAMA neurology. 2018. doi:10.1001/jamaneurol.2018.3139. PMID: 30422173.

BibTeX

@article{wennberg2018-30422173,
  author  = {Wennberg, A. M. and Tosakulwong, N. and Lesnick, T. G. and Murray, M. E. and Whitwell, J. L. and Liesinger, A. M. and Petrucelli, L. and Boeve, B. F. and others},
  title   = {{Association of Apolipoprotein E ε4 With Transactive Response DNA-Binding Protein 43}},
  journal = {JAMA neurology},
  year    = {2018},
  doi     = {10.1001/jamaneurol.2018.3139},
  pmid    = {30422173},
  url     = {https://doi.org/10.1001/jamaneurol.2018.3139}
}

Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.

Key findings

Importance Transactive response DNA-binding protein 43 (TDP-43) is associated with Alzheimer disease (AD), progressive hippocampal atrophy, and cognitive decline.
The apolipoprotein E (APOE) ε4 allele is strongly associated with β-amyloid (Aβ) aggregation and risk of AD, but its association with TDP-43 is unknown.
We hypothesized that the APOE ε4 allele would be significantly directly and indirectly associated with TDP-43.
Results The 751 study participants were older (median age [interquartile range], 87 years [51-105 years]), 395 (54%) were women, and 324 (44%) were APOE ε4 carriers.
The association was present among individuals with an intermediate to high likelihood of having AD (neurofibrillary tangle stage B2/B3; n = 604 [81.8%]; estimate [SE], 0.51 [0.11]; P < .001), with a similar trend for those with a low likelihood of having AD (B1; n = 134 [18.2%]; estimate [SE], 0.54 [0.32]; P = .10).

Why it matters

In 738 autopsied people from Mayo Clinic research programmes who had Alzheimer-type brain changes, carrying the APOE ε4 gene variant was linked to TDP-43, a protein associated with hippocampal shrinkage and cognitive decline. The link was statistically significant in people whose brains had intermediate-to-high Alzheimer's likelihood (604 people), but not in the smaller low-likelihood group (134 people, P = .10). This is an association from brain tissue after death, not proof that ε4 causes TDP-43 build-up, and it reports no treatment or prevention.

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

Study details

Study designcross-sectional
Participants604
Effect size81.8%
Evidence strengthLow

How this study scored 59/100

Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for randomised / blinded because the record does not state it.

Component	Points	Why
Journal tier	9 / 10	Tier 2 — leading specialty journal (JAMA neurology)
Journal's citation record	2 / 4	JAMA Neurology: journal h-index 235 (OpenAlex, 2026-10-29)
Study design	4 / 12	A snapshot of people at one point in time
Strength of evidence	1 / 5	Rated “low” in our summary
Peer-review validation	10 / 10	Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent	2 / 5	2018 — within 10 year(s) of the newest study here
Sample size	2 / 4	604 participants
Effect reported	2 / 3	Effect reported as a number, without an interval or test
Studied in people	3 / 3	Studied in people (participant count stated)
Randomised / blinded	0 / 2	No randomisation or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	4 / 7	Cited 97 times (OpenAlex, 2026-10-10)
Citations per year	3 / 5	9.7 citations a year over 10 year(s) since 2018
Impact for its field and year	3 / 6	Cited 5.8× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	3 / 6	Cited by 11 other studies in this library
Still being cited	2 / 4	Cited 32 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	4 / 4	Last-listed author Keith A. Josephs: h-index 119 (OpenAlex, whole career)
Institution's track record	2 / 3	Mayo Clinic: institution h-index 1,606 (OpenAlex)
Multi-centre collaboration	1 / 3	OpenAlex lists 2 institution(s) in 1 country
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 30422173)
Free to read	0 / 2	Behind a paywall — scores zero
Total	59 / 100	—

What each of these 20 components measures, and what this score is not →

Read the original

Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 18.

Later studies that cite this one

11 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.

Related studies in Genetics

Also tagged “tdp-43”

1,150 studies in the library carry the topic tag “tdp-43”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,150 tagged studies.

Similar studies

More on Genetics

See all studies in Genetics →