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Locus coeruleus TDP-43 pathology in a community-based cohort: Clinical and pathological correlates
Allison M. Neltner, Ryan K. Shahidehpour, Megan E. Hall, Xiaotong Ning, Shuling X. Fister, Hannah Kang, Sonya L. Anderson, Gregory A. Jicha et al.. Journal of Neuropathology & Experimental Neurology, 2026-03-24
Topic: Brain proteins, microglia and lab models
The locus coeruleus (LC) is the source of norepinephrinergic innervation in the human brain. Locus coeruleus pathology has been linked to clinical conditions such as cognitive impairment and behavioral and psychiatric symptoms of dementia (BPSD). However, phosphorylated TDP-43 (pTDP-43) pathology in the LC has been understudied, particularly in the contexts of aging and limbic predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). Here, a convenience sample (n = 134) of autopsied participants from the University of Kentucky Alzheimer's Disease Research Center community-based cohort was analyzed for LC pTDP-43 and phosphorylated tau (pTau) pathologies. Locus coeruleus pTDP-43 pathology was found in 28/134 (20.9%) brains and was generally sparse when present. Locus coeruleus pTDP-43 lesions typically appeared as round granular structures that measured ∼3-12 µm in diameter. Locus coeruleus pTDP-43 pathology was increased with aging and was imperfectly correlated with LATE-NC staging; it showed no correlation with cortical pTau pathology in ADNC or PART. In terms of clinical-pathological correlations, LC pTDP-43 pathology was associated with depressive symptoms but not with global cognition or with other BPSDs. Locus coeruleus pTau pathology was positively correlated with cortical pTau pathologic severity and with LATE-NC stages. In conclusion, LC pTDP-43 pathology is a common feature of brain aging, associated with LATE-NC.
Key findings
- In terms of clinical-pathological correlations, LC pTDP-43 pathology was associated with depressive symptoms but not with global cognition or with other BPSDs.
- In conclusion, LC pTDP-43 pathology is a common feature of brain aging, associated with LATE-NC.
Why it matters
In this community-based cohort of 134 autopsied participants, locus coeruleus pTDP-43 pathology was found in about 21% of brains and was associated with depressive symptoms but not with global cognition. This suggests LC pTDP-43 pathology is a common feature of brain aging associated with LATE-NC, but its clinical significance for cognition is limited.
Study details
- Participants134
- Effect size20.9%
- Evidence strengthModerate
How this study scored 46/100
Published in a peer-reviewed journal. Scored zero for study design and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Neuropathology & Experimental Neurology) |
| Journal's citation record | 2 / 4 | Journal of Neuropathology & Experimental Neurology: journal h-index 239 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 2 / 4 | 134 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 | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 3 / 6 | Cited 4.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Peter T. Nelson: h-index 92 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Kentucky: institution h-index 824 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42008717) |
| Free to read | 2 / 2 | Free to read |
| Total | 46 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1093/jnen/nlag035
- PubMed: 42008717
- Original source →
- Free full text: Journal of Neuropathology & Experimental Neurology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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.
APA 7th
Neltner, A. M., Shahidehpour, R. K., Hall, M. E., Ning, X., Fister, S. X., Kang, H., et al. (2026). Locus coeruleus TDP-43 pathology in a community-based cohort: Clinical and pathological correlates. Journal of Neuropathology & Experimental Neurology. https://doi.org/10.1093/jnen/nlag035
Vancouver
Neltner AM, Shahidehpour RK, Hall ME, Ning X, Fister SX, Kang H, et al. Locus coeruleus TDP-43 pathology in a community-based cohort: Clinical and pathological correlates. Journal of Neuropathology & Experimental Neurology. 2026. doi:10.1093/jnen/nlag035. PMID: 42008717.
BibTeX
@article{neltner2026-42008717,
author = {Neltner, Allison M. and Shahidehpour, Ryan K. and Hall, Megan E. and Ning, Xiaotong and Fister, Shuling X. and Kang, Hannah and Anderson, Sonya L. and Jicha, Gregory A. and others},
title = {{Locus coeruleus TDP-43 pathology in a community-based cohort: Clinical and pathological correlates}},
journal = {Journal of Neuropathology \& Experimental Neurology},
year = {2026},
doi = {10.1093/jnen/nlag035},
pmid = {42008717},
url = {https://doi.org/10.1093/jnen/nlag035}
}
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