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TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease
Amador-Ortiz C, Lin WL, Ahmed Z, Personett D, Davies P, Duara R, Graff-Radford NR, Hutton ML et al.. Annals of neurology, 2007-05-01
Topic: Brain proteins, microglia and lab models
Objective This study aimed to determine the frequency of frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) in the setting of hippocampal sclerosis (HpScl) and Alzheimer's disease (AD) using immunohistochemistry for TAR DNA binding protein 43 (TDP-43), a putative marker for FTLD-U. Methods Initially, 21 cases of HpScl associated with a variety of other pathological processes and 74 cases of AD were screened for FTLD-U with TDP-43 immunohistochemistry. A confirmation study was performed on 93 additional AD cases. Specificity of TDP-43 antibodies was assessed using double-immunolabeling confocal microscopy, immunoelectron microscopy, and biochemistry. Results TDP-43 immunoreactivity was detected in 71% of HpScl and 23% of AD cases. Double immunostaining of AD cases for TDP-43 and phospho-tau showed that the TDP-43-immunoreactive inclusions were usually distinct from neurofibrillary tangles. At the ultrastructural level, TDP-43 immunoreactivity in AD was associated with granular and filamentous cytosolic material and only occasionally associated with tau filaments. Western blots of AD cases showed a band that migrated at a higher molecular weight than normal TDP-43 that was not present in AD cases without TDP-43 immunoreactivity. Interpretation These results suggest that as many as 20% of AD cases and more than 70% of HpScl cases have pathology similar to that found in FTLD-U. Whether this represents concomitant FTLD-U or is analogous to colocalization of alpha-synuclein and tau in AD, reflecting a propensity for codeposition of abnormal protein conformers, remains to be determined.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Amador-Ortiz, C., Lin, W. L., Ahmed, Z., Personett, D., Davies, P., Duara, R., et al. (2007). TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease. Annals of neurology. https://doi.org/10.1002/ana.21154
Vancouver
Amador-Ortiz C, Lin WL, Ahmed Z, Personett D, Davies P, Duara R, et al. TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease. Annals of neurology. 2007. doi:10.1002/ana.21154. PMID: 17469117.
BibTeX
@article{amadorortiz2007-17469117,
author = {Amador-Ortiz, C. and Lin, W. L. and Ahmed, Z. and Personett, D. and Davies, P. and Duara, R. and Graff-Radford, N. R. and Hutton, M. L. and others},
title = {{TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease}},
journal = {Annals of neurology},
year = {2007},
doi = {10.1002/ana.21154},
pmid = {17469117},
url = {https://doi.org/10.1002/ana.21154}
}
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Key findings
- Methods Initially, 21 cases of HpScl associated with a variety of other pathological processes and 74 cases of AD were screened for FTLD-U with TDP-43 immunohistochemistry.
- Results TDP-43 immunoreactivity was detected in 71% of HpScl and 23% of AD cases.
- Double immunostaining of AD cases for TDP-43 and phospho-tau showed that the TDP-43-immunoreactive inclusions were usually distinct from neurofibrillary tangles.
- At the ultrastructural level, TDP-43 immunoreactivity in AD was associated with granular and filamentous cytosolic material and only occasionally associated with tau filaments.
- Interpretation These results suggest that as many as 20% of AD cases and more than 70% of HpScl cases have pathology similar to that found in FTLD-U.
Why it matters
In brain tissue from people who had died, TDP-43 protein clumps were found in 71% of cases with hippocampal sclerosis and 23% of Alzheimer's disease cases. This suggests that some Alzheimer's cases have a pathology similar to frontotemporal lobar degeneration with ubiquitinated inclusions, but it is a tissue study and does not test treatment or prevention.
Study details
- Evidence strengthLow
How this study scored 56/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Annals of neurology) |
| Journal's citation record | 3 / 4 | Annals of Neurology: journal h-index 437 (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 | 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 | 1 / 5 | 2007 — within 20 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 923 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 44.0 citations a year over 21 year(s) since 2007 |
| Impact for its field and year | 5 / 6 | Cited 35.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 83 other studies in this library |
| Still being cited | 3 / 4 | Cited 154 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Dennis W. Dickson: h-index 218 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 17469117) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 56 / 100 | — |
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