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Phenotypic variability in early-onset dementia segregating with a novel APP (p.I718M) variant
Johansson C, Rodriguez-Vieitez E, Bluma M, Nennesmo I, Thonberg H, Ullgren A, Jelic V, Zetterberg H et al.. Alzheimer's research & therapy, 2025-12-01
Topic: Amyloid, tau and blood-test diagnosis
BACKGROUND: Autosomal dominant Alzheimer disease (ADAD) is caused by pathogenic variants in the APP, PSEN1 and PSEN2 genes, but a substantial fraction of reported variants is of unknown clinical significance. Here we report a novel variant in the amyloid precursor protein gene (APP p.I718M). METHODS: Five siblings from a family with a multi-generational history of cognitive disease were assessed for cognitive impairment at the memory clinic at Karolinska University Hospital.
Key findings
- Here we report a novel variant in the amyloid precursor protein gene (APP p.I718M).
- METHODS: Five siblings from a family with a multi-generational history of cognitive disease were assessed for cognitive impairment at the memory clinic at Karolinska University Hospital.
- Data were included for genetic analysis, segregation analysis, phenotyping and fluid biomarker analysis.
- Biomarker analyses were performed in CSF (Aβ38, Aβ40, Aβ42, t-tau, p-tau181, NfL) and plasma (p-tau181, p-tau217, GFAP, NfL).
Why it matters
This report describes five siblings from one family with a novel APP p.I718M variant and varied early-onset dementia symptoms. It adds information about a possible genetic cause of autosomal dominant Alzheimer disease, but does not test or offer any treatment, cure or prevention.
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Study details
- Evidence strengthLow
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 randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer's research & therapy) |
| Journal's citation record | 1 / 4 | Alzheimer s Research & Therapy: journal h-index 146 (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 | 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 | 3 / 4 | Last-listed author Caroline Graff: h-index 79 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 13 institution(s) in 5 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41327373) |
| 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
- DOI: 10.1186/s13195-025-01890-9
- PubMed: 41327373
- Original source →
- Free full text: Alzheimer s Research & Therapy →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Johansson, C., Rodriguez-Vieitez, E., Bluma, M., Nennesmo, I., Thonberg, H., Ullgren, A., et al. (2025). Phenotypic variability in early-onset dementia segregating with a novel APP (p.I718M) variant. Alzheimer's research & therapy. https://doi.org/10.1186/s13195-025-01890-9
Vancouver
Johansson C, Rodriguez-Vieitez E, Bluma M, Nennesmo I, Thonberg H, Ullgren A, et al. Phenotypic variability in early-onset dementia segregating with a novel APP (p.I718M) variant. Alzheimer's research & therapy. 2025. doi:10.1186/s13195-025-01890-9. PMID: 41327373.
BibTeX
@article{johansson2025-41327373,
author = {Johansson, C. and Rodriguez-Vieitez, E. and Bluma, M. and Nennesmo, I. and Thonberg, H. and Ullgren, A. and Jelic, V. and Zetterberg, H. and others},
title = {{Phenotypic variability in early-onset dementia segregating with a novel APP (p.I718M) variant}},
journal = {Alzheimer's research \& therapy},
year = {2025},
doi = {10.1186/s13195-025-01890-9},
pmid = {41327373},
url = {https://doi.org/10.1186/s13195-025-01890-9}
}
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