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TDP-43 proteinopathy: the complex biological and clinical findings in LATE-NC, LANS, and other mixed age-related major neurocognitive disorders
Márcia Radanovic, Carlos Eduardo Borges Passos Neto, L.H.A. Monteiro, Orestes Vicente Forlenza. Current Opinion in Psychiatry, 2025-07-15
Topic: Brain proteins, microglia and lab models
PURPOSE OF REVIEW: Since the term limbic-predominant age-related TDP-43 encephalopathy (LATE) was coined in 2019, more than 200 articles addressing the subject were published. This review aims to provide an updated synthesis of knowledge regarding LATE-NC as a cause of age-related neurodegeneration and cognitive decline while addressing the challenges posed by overlapping neuropathologies in aging populations. RECENT FINDINGS: LATE-NC is marked by TDP-43 deposition in limbic structures, such as the amygdala and hippocampus, and is often associated with cognitive decline resembling Alzheimer's disease, though with a slower progression in isolated cases. The frequent coexistence of LATE-NC with other neuropathologies, particularly Alzheimer's disease neuropathologic changes (ADNC) and Lewy body dementia (LBD), exacerbates dementia severity and complicates diagnosis and treatment. Recent efforts have established clinical criteria for in-vivo diagnosis, including neuroimaging markers like hippocampal atrophy and limbic hypometabolism. Genetic studies have identified key risk genes, including GRN , TMEM106B , SORL1 , and APOE , while biomarker development in cerebrospinal fluid (CSF) and blood remains in its early stages. SUMMARY: The review underscores the need for multidisciplinary research and clinical approaches to address the complexities of neurodegenerative diseases involving TDP-43 proteinopathy, improve diagnostic accuracy, and develop effective treatments tailored to individual patient profiles.
Key findings
- RECENT FINDINGS: LATE-NC is marked by TDP-43 deposition in limbic structures, such as the amygdala and hippocampus, and is often associated with cognitive decline resembling Alzheimer's disease, though with a slower progression in isolated cases.
Why it matters
This review describes LATE-NC as a cause of age-related cognitive decline that often coexists with other neuropathologies like Alzheimer's disease changes and Lewy body dementia. It notes that clinical criteria for in-vivo diagnosis have been established and that biomarker development in CSF and blood remains in its early stages.
Study details
- Evidence strengthLow
How this study scored 32/100
Published in a peer-reviewed 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 | 7 / 10 | Tier 3 — peer-reviewed journal (Current Opinion in Psychiatry) |
| Journal's citation record | 1 / 4 | Current Opinion in Psychiatry: journal h-index 141 (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 | 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) |
| 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 | 0.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 1 / 6 | Cited 0.6× 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 Orestes Vicente Forlenza: h-index 67 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Universidade de São Paulo: institution h-index 936 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40709644) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 32 / 100 | — |
What each of these 20 components measures, and what this score is not →
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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. Check the citation against the original before you use it.
APA 7th
Radanovic, M., Neto, C. E. B. P., Monteiro, L., & Forlenza, O. V. (2025). TDP-43 proteinopathy: the complex biological and clinical findings in LATE-NC, LANS, and other mixed age-related major neurocognitive disorders. Current Opinion in Psychiatry. https://doi.org/10.1097/yco.0000000000001027
Vancouver
Radanovic M, Neto CEBP, Monteiro L, Forlenza OV. TDP-43 proteinopathy: the complex biological and clinical findings in LATE-NC, LANS, and other mixed age-related major neurocognitive disorders. Current Opinion in Psychiatry. 2025. doi:10.1097/yco.0000000000001027. PMID: 40709644.
BibTeX
@article{radanovic2025-40709644,
author = {Radanovic, Márcia and Neto, Carlos Eduardo Borges Passos and Monteiro, L.H.A. and Forlenza, Orestes Vicente},
title = {{TDP-43 proteinopathy: the complex biological and clinical findings in LATE-NC, LANS, and other mixed age-related major neurocognitive disorders}},
journal = {Current Opinion in Psychiatry},
year = {2025},
doi = {10.1097/yco.0000000000001027},
pmid = {40709644},
url = {https://doi.org/10.1097/yco.0000000000001027}
}
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