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43/100

✓ Peer-reviewed alzhub usefulness score 43 out of 100. Brain tissue and pathology

Topic: Amyloid, tau and blood-test diagnosis

Plain-language summary

Copy number variation (CNV) of the amyloid-β precursor protein gene (APP) is a known cause of autosomal dominant Alzheimer disease (ADAD), but de novo genetic variants causing ADAD are rare. We report a mother and daughter with neuropathologically confirmed definite Alzheimer disease (AD) and extensive cerebral amyloid angiopathy (CAA). Copy number analysis identified an increased number of APP copies and genome sequencing (GS) revealed the underlying complex genomic rearrangement (CGR) including a triplication of APP with two unique breakpoint junctions (BPJs). The mosaic state in the mother had likely occurred de novo. Digital droplet PCR (ddPCR) on 42 different tissues, including 17 different brain regions, showed the derivative chromosome at varying mosaic levels (20-96%) in the mother who had symptom onset at age 58 years. In contrast, the derivative chromosome was present in all analyzed cells in the daughter whose symptom onset was at 34 years. This study reveals the architecture of a de novo CGR causing APP triplication and ADAD with a striking difference in age at onset between the fully heterozygous daughter compared to the mosaic mother. The GS analysis identified the complexity of the CGR illustrating its usefulness in identifying structural variants (SVs) in neurodegenerative disorders.

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APA 7th

Ehn, E., Eisfeldt, J., Laffita‐Mesa, J. M., Thonberg, H., Schoumans, J., Portaankorva, A. M., et al. (2025). A de novo, mosaic and complex chromosome 21 rearrangement causes APP triplication and familial autosomal dominant early onset Alzheimer disease. Scientific Reports. https://doi.org/10.1038/s41598-025-86645-0

Vancouver

Ehn E, Eisfeldt J, Laffita‐Mesa JM, Thonberg H, Schoumans J, Portaankorva AM, et al. A de novo, mosaic and complex chromosome 21 rearrangement causes APP triplication and familial autosomal dominant early onset Alzheimer disease. Scientific Reports. 2025. doi:10.1038/s41598-025-86645-0. PMID: 39849058.

BibTeX

@article{ehn2025-39849058,
  author  = {Ehn, Emma and Eisfeldt, Jesper and Laffita‐Mesa, José Miguel and Thonberg, Håkan and Schoumans, Jacqueline and Portaankorva, Anne M. and Viitanen, Matti H. and Lindstrand, Anna and others},
  title   = {{A de novo, mosaic and complex chromosome 21 rearrangement causes APP triplication and familial autosomal dominant early onset Alzheimer disease}},
  journal = {Scientific Reports},
  year    = {2025},
  doi     = {10.1038/s41598-025-86645-0},
  pmid    = {39849058},
  url     = {https://doi.org/10.1038/s41598-025-86645-0}
}

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How to read this study

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What the evidence grade means here

This page is graded low. alzhub.org assigns the grade automatically from keywords in the abstract, not from reading the paper. Low means the abstract matched neither pattern. It is the default label, and it does not mean the work is poor; many sound lab and imaging papers land here. It can add at most 5 of the 100 points in the study score, and it is a label about design, not a verdict on whether the findings are true.

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Key findings

Copy number analysis identified an increased number of APP copies and genome sequencing (GS) revealed the underlying complex genomic rearrangement (CGR) including a triplication of APP with two unique breakpoint junctions (BPJs).
This study reveals the architecture of a de novo CGR causing APP triplication and ADAD with a striking difference in age at onset between the fully heterozygous daughter compared to the mosaic mother.

Why it matters

This report describes a mother and daughter with a rare, complex rearrangement of chromosome 21 that tripled the APP gene and caused early-onset inherited Alzheimer's disease, with symptoms starting at age 58 in the mother and 34 in the daughter. It shows how detailed genome analysis can identify such structural changes, but it does not offer a treatment.

Study details

Evidence strengthLow

How this study scored 43/100

Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (Scientific Reports)
Journal's citation record	3 / 4	Scientific Reports: journal h-index 463 (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)
Randomized / blinded	0 / 2	No randomization or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	2 / 7	Cited 8 times (OpenAlex, 2026-10-10)
Citations per year	1 / 5	2.7 citations a year over 3 year(s) since 2025
Impact for its field and year	3 / 6	Cited 4.4× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	1 / 6	Cited by 1 other studies in this library
Still being cited	1 / 4	Cited 8 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	1 / 3	Karolinska Institutet: institution h-index 1,477 (OpenAlex)
Multicenter collaboration	2 / 3	OpenAlex lists 4 institution(s) in 3 countries
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 39849058)
Free to read	2 / 2	Free to read
Total	43 / 100	—

What each of these 20 components measures, and what this score is not →

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