Home › Research › Brain tissue and pathology
Assessing Co‐Localization of ITM2B With Alzheimer's Disease and Limbic‐Predominant Age‐Related TDP ‐43 Encephalopathy Neuropathologic Changes
Ryan K. Shahidehpour, Peter T. Nelson, Sukanya Srinivasan, Yu Zhong, Adam D. Bachstetter. Neuropathology, 2025-03-05
Topic: Brain proteins, microglia and lab models
Mutations in the Integral membrane protein 2B (ITM2B) gene are linked to the development of familial British and Danish dementias, two relatively early-onset dementia disorders known also to be associated with Tau neurofibrillary tangles (NFTs). However, to date, the involvement of ITM2B in limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC) remains unclear. To address this question, we used brain samples from the University of Kentucky Alzheimer's Disease Research Center community-based autopsy cohort. We investigated the patterns and co-localizations of ITM2B immunohistochemistry in subiculum, CA1, CA2, CA3 and dentate gyrus of the hippocampus from brains with Alzheimer's disease neuropathologic changes (ADNC), LATE-NC, and comorbid ADNC+LATE-NC, as well as low-pathology controls (n = 4 per disease state). There was frequent co-localization between ITM2B protein and intracellular Tau pathology in ADNC; however, there was a far weaker rate of co-localization between ITM2B and TDP-43 pathology. There also was, as previously described, an association between ITM2B immunostaining and neuritic-appearing amyloid plaques. Additionally, co-localization of intracellular ITM2B pathology with Thioflavin-S in NFTs suggested a potential role for ITM2B in marking neurons undergoing transition from relatively healthy (early NFT-bearing cells) to more severely affected (later NFT-bearing) cellular disease states. This study indicates that ITM2B has a relatively specific pattern of involvement in Tau-related neurodegeneration and in neuritic amyloid plaques, while implying minimal, if any, role for ITM2B in the synergistic relationship between Tau and TDP-43 pathologies.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Shahidehpour, R. K., Nelson, P. T., Srinivasan, S., Zhong, Y., & Bachstetter, A. D. (2025). Assessing Co‐Localization of ITM2B With Alzheimer's Disease and Limbic‐Predominant Age‐Related TDP ‐43 Encephalopathy Neuropathologic Changes. Neuropathology. https://doi.org/10.1111/neup.70003
Vancouver
Shahidehpour RK, Nelson PT, Srinivasan S, Zhong Y, Bachstetter AD. Assessing Co‐Localization of ITM2B With Alzheimer's Disease and Limbic‐Predominant Age‐Related TDP ‐43 Encephalopathy Neuropathologic Changes. Neuropathology. 2025. doi:10.1111/neup.70003. PMID: 40042444.
BibTeX
@article{shahidehpour2025-40042444,
author = {Shahidehpour, Ryan K. and Nelson, Peter T. and Srinivasan, Sukanya and Zhong, Yu and Bachstetter, Adam D.},
title = {{Assessing Co‐Localization of ITM2B With Alzheimer's Disease and Limbic‐Predominant Age‐Related TDP ‐43 Encephalopathy Neuropathologic Changes}},
journal = {Neuropathology},
year = {2025},
doi = {10.1111/neup.70003},
pmid = {40042444},
url = {https://doi.org/10.1111/neup.70003}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- Mutations in the Integral membrane protein 2B (ITM2B) gene are linked to the development of familial British and Danish dementias, two relatively early-onset dementia disorders known also to be associated with Tau neurofibrillary tangles (NFTs).
- This study indicates that ITM2B has a relatively specific pattern of involvement in Tau-related neurodegeneration and in neuritic amyloid plaques, while implying minimal, if any, role for ITM2B in the synergistic relationship between Tau and TDP-43 pathologies.
Why it matters
This study used a small number of brain samples (n = 4 per disease state) and found that ITM2B co-localized frequently with tau pathology but far less with TDP-43 pathology. This suggests ITM2B has little if any role in the relationship between tau and TDP-43, so it is not a promising treatment target for that interaction.
Study details
- Evidence strengthModerate
How this study scored 35/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neuropathology) |
| Journal's citation record | 1 / 4 | Neuropathology: journal h-index 83 (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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 2 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.1× 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 2 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Adam D. Bachstetter: h-index 48 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Kentucky: institution h-index 824 (OpenAlex) |
| Multicenter 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 40042444) |
| Free to read | 2 / 2 | Free to read |
| Total | 35 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Related
Studies in the library that share something with this one. The line above each title says what.
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Related studies in Brain tissue and pathology
Also tagged “machine”
834 studies in the library carry the topic tag “machine”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 834 tagged studies.