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Challenges in the identification of underlying pathologies in dementias with predominant behavioral phenotype using laboratory biomarkers
Kseniya V. Nevzorova, Yu. A. Shpilyukova, Alla A. Shabalina, Natalya Abramycheva, Lusine A. Brsikyan, Ekaterina Yu. Fedotova, Sergey Nikolaevich Illarioshkin. Alzheimer s & Dementia, 2025-12-01
Topic: Amyloid, tau and blood-test diagnosis
Abstract Background Predominant behavioral forms of dementias are usually associated with frontotemporal lobar degeneration (FTLD) spectrum and considerably less often with atypical Alzheimer's disease (AD). The most common and clinically available genetic biomarker of FTLD is a repeat expansion in C9orf72 , which is associated with TDP‐43 pathology. Biomarkers of Alzheimer pathology in accordance with the IWG recommendations (Dubois et al., 2021) are Abeta‐42 and p ‐tau181 in cerebrospinal fluid (CSF). The aim of our study was to evaluate these biomarkers in a cohort of patients with predominant behavioral symptoms. Method We examined 20 patients (9 females and 11 males, median age 64.5 [58; 72] years, median disease duration 4 [2; 5] years) with predominant behavioral impairments meeting clinical criteria of possible/probable behavioral variant of frontotemporal demetia (bvFTD) (Rascovsky et al., 2011). Positive family history of cognitive impairments was detected in 11 cases (55%). All patients underwent blood sampling for DNA testing of C9orf72 repeat expansion (repeat‐primed PCR), and lumbar puncture for assessment of Abeta‐42 and p ‐tau181 biomarkers in CSF (ELISA). Result We found 3 patients (15%) with hexanucleotide repeat expansions in C9orf72 , which allowed us to diagnose bvFTD with definite FTLD‐TDP pathology. Two of these patients (10%) additionally had a low level of CSF Abeta‐42 assuming a verified overlap of AD and FTLD‐TDP pathologies. Among C9orf72 ‐negative patients positive biomarkers of AD pathology was detected in 8 cases (40% of all group) including 4 patients with probable AD diagnosis and 4 with possible AD. As a result in the whole cohort we found 50% cases with AD pathology, which could coexist with FTLD pathology or could be possibly isolated. Nine patients (45%) had no pathological AD changes in CSF and no C9orf72 repeat expansion. In these cases underlying pathologies could belong to a classic FTLD spectrum including tau, TDP, FUS. Conclusion Neurodegenerative dementias with behavioral clinical presentation are a diverse group of diseases. In this study we showed the presence of not uncommon cases with overlapping pathologies. This highlights the importance and the need of a wide variety of laboratory tests available for clinical use in order to accurately predict in vivo underlying pathologies.
Key findings
- Abstract Background Predominant behavioral forms of dementias are usually associated with frontotemporal lobar degeneration (FTLD) spectrum and considerably less often with atypical Alzheimer's disease (AD).
- The most common and clinically available genetic biomarker of FTLD is a repeat expansion in C9orf72 , which is associated with TDP‐43 pathology.
- Result We found 3 patients (15%) with hexanucleotide repeat expansions in C9orf72 , which allowed us to diagnose bvFTD with definite FTLD‐TDP pathology.
- As a result in the whole cohort we found 50% cases with AD pathology, which could coexist with FTLD pathology or could be possibly isolated.
Why it matters
In 20 patients with predominant behavioral symptoms, 3 (15%) had C9orf72 repeat expansions confirming FTLD-TDP pathology, and 2 of these also had low levels of Alzheimer's biomarkers. The study highlights challenges in identifying underlying pathologies in dementias with behavioral symptoms using laboratory biomarkers, and does not report any treatment, prevention or cure for Alzheimer's disease.
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Study details
- Participants20
- Evidence strengthModerate
How this study scored 35/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (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 | 1 / 4 | 20 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 | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 0 / 6 | Cited 0.0× 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 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Sergey Nikolaevich Illarioshkin: h-index 31 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Research Center of Neurology: institution h-index 80 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Total | 35 / 100 | — |
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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. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Nevzorova, K. V., Shpilyukova, Y. A., Shabalina, A. A., Abramycheva, N., Brsikyan, L. A., Fedotova, E. Y., et al. (2025). Challenges in the identification of underlying pathologies in dementias with predominant behavioral phenotype using laboratory biomarkers. Alzheimer s & Dementia. https://doi.org/10.1002/alz70856_106350
Vancouver
Nevzorova KV, Shpilyukova YA, Shabalina AA, Abramycheva N, Brsikyan LA, Fedotova EY, et al. Challenges in the identification of underlying pathologies in dementias with predominant behavioral phenotype using laboratory biomarkers. Alzheimer s & Dementia. 2025. doi:10.1002/alz70856_106350.
BibTeX
@article{nevzorova2025-a216cab1,
author = {Nevzorova, Kseniya V. and Shpilyukova, Yu. A. and Shabalina, Alla A. and Abramycheva, Natalya and Brsikyan, Lusine A. and Fedotova, Ekaterina Yu. and Illarioshkin, Sergey Nikolaevich},
title = {{Challenges in the identification of underlying pathologies in dementias with predominant behavioral phenotype using laboratory biomarkers}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz70856_106350},
url = {https://doi.org/10.1002/alz70856_106350}
}