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TDP-43 stage, mixed pathologies, and clinical Alzheimer's-type dementia
James BD, Wilson RS, Boyle PA, Trojanowski JQ, Bennett DA, Schneider JA.. Brain : a journal of neurology, 2016-11-01
Topic: Amyloid, tau and blood-test diagnosis
We tested the hypotheses that TDP-43 with Alzheimer's disease pathology is a common mixed pathology; is related to increased likelihood of expressing clinical Alzheimer's-type dementia; and that TDP-43 pathologic stage is an important determinant of clinical Alzheimer's-type dementia. In logistic regression models adjusted for age, sex, and education, TDP-43 pathology was associated with clinical Alzheimer's-type dementia (odds ratio = 1.51, 95% confidence interval = 1.11, 2.05) independent of pathological Alzheimer's disease (odds ratio = 4.30, 95% confidence interval = 3.08, 6.01) or other pathologies (infarcts, arteriolosclerosis, Lewy bodies, and hippocampal sclerosis). Mixed Alzheimer's disease and TDP-43 pathologies were associated with higher odds of clinical Alzheimer's-type dementia (odds ratio = 6.73, 95% confidence interval = 4.18, 10.85) than pathologic Alzheimer's disease alone (odds ratio = 4.62, 95% confidence interval = 2.84, 7.52). In models examining TDP-43 stage, a dose-response relationship with clinical Alzheimer's-type dementia was observed, and a significant association was observed starting at stage 2, extension beyond the amygdala. In this large sample from almost 1000 community participants, we observed that TDP-43 proteinopathy was very common, frequently mixed with pathological Alzheimer's disease, and associated with a higher likelihood of the clinical expression of clinical Alzheimer's-type dementia but only when extended beyond the amygdala.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
James, B. D., Wilson, R. S., Boyle, P. A., Trojanowski, J. Q., Bennett, D. A., & Schneider, J. A. (2016). TDP-43 stage, mixed pathologies, and clinical Alzheimer's-type dementia. Brain : a journal of neurology. https://doi.org/10.1093/brain/aww224
Vancouver
James BD, Wilson RS, Boyle PA, Trojanowski JQ, Bennett DA, Schneider JA. TDP-43 stage, mixed pathologies, and clinical Alzheimer's-type dementia. Brain : a journal of neurology. 2016. doi:10.1093/brain/aww224. PMID: 27694152.
BibTeX
@article{james2016-27694152,
author = {James, B. D. and Wilson, R. S. and Boyle, P. A. and Trojanowski, J. Q. and Bennett, D. A. and Schneider, J. A.},
title = {{TDP-43 stage, mixed pathologies, and clinical Alzheimer's-type dementia}},
journal = {Brain : a journal of neurology},
year = {2016},
doi = {10.1093/brain/aww224},
pmid = {27694152},
url = {https://doi.org/10.1093/brain/aww224}
}
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Key findings
- We tested the hypotheses that TDP-43 with Alzheimer's disease pathology is a common mixed pathology; is related to increased likelihood of expressing clinical Alzheimer's-type dementia; and that TDP-43 pathologic stage is an important determinant of clinical Alzheimer's-type dementia.
- In logistic regression models adjusted for age, sex, and education, TDP-43 pathology was associated with clinical Alzheimer's-type dementia (odds ratio = 1.51, 95% confidence interval = 1.11, 2.05) independent of pathological Alzheimer's disease (odds ratio = 4.30, 95% confidence interval = 3.08, 6.01) or other pathologies (infarcts, arteriolosclerosis, Lewy bodies, and hippocampal sclerosis).
- Mixed Alzheimer's disease and TDP-43 pathologies were associated with higher odds of clinical Alzheimer's-type dementia (odds ratio = 6.73, 95% confidence interval = 4.18, 10.85) than pathologic Alzheimer's disease alone (odds ratio = 4.62, 95% confidence interval = 2.84, 7.52).
- In models examining TDP-43 stage, a dose-response relationship with clinical Alzheimer's-type dementia was observed, and a significant association was observed starting at stage 2, extension beyond the amygdala.
- In this large sample from almost 1000 community participants, we observed that TDP-43 proteinopathy was very common, frequently mixed with pathological Alzheimer's disease, and associated with a higher likelihood of the clinical expression of clinical Alzheimer's-type dementia but only when extended beyond the amygdala.
Why it matters
In almost 1000 community participants, TDP-43 protein pathology was "very common" and "frequently mixed" with Alzheimer's disease pathology. After adjusting for age, sex and education, TDP-43 pathology was linked to higher odds of a clinical diagnosis of Alzheimer's-type dementia (odds ratio 1.51), independent of Alzheimer's pathology and other brain changes, and the link was significant only once TDP-43 had spread "beyond the amygdala" (stage 2 onward). This is an association, so it suggests other brain changes add to the dementia diagnosed as Alzheimer's; it does not show cause or point to a treatment.
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Study details
- Participants398
- Evidence strengthModerate
How this study scored 63/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (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 | 1 / 5 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 398 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 407 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 33.9 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 5 / 6 | Cited 25.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 38 other studies in this library |
| Still being cited | 3 / 4 | Cited 110 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Julie A. Schneider: h-index 151 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Pennsylvania: institution h-index 1,859 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 27694152) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 63 / 100 | — |
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