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Cryo‐EM structures of amyloid β filaments from cotton wool plaques in Alzheimer disease caused by the PSEN1 V261I and A431E mutations
Anllely Fernández, Md Rejaul Hoq, Frank S. Vago, Grace I. Hallinan, S.R. Bharath, Daoyi Li, Kadir A. Ozcan, Holly J. Garringer et al.. Alzheimer s & Dementia, 2025-12-01
Topic: Brain proteins, microglia and lab models
CWPs consist predominantly of two novel arrangements of type I Aβ filaments, and we have designated them as type Ic and type Id Aβ filaments. The latter filaments exhibit unique protofilament packing arrangements. While the type Ic Aβ filaments share a largely similar S-shaped monomeric configuration with type I Aβ filaments, type Id Aβ filaments display an antiparallel and asymmetric packing, in contrast to the twofold parallel arrangement characteristic of type Ib and Ic Aβ filaments. The formation of type Ic and type Id Aβ filaments in CWPs may be linked to a distinct array of Aβ peptide species present in CWPs, differing from those found in core plaques in sporadic AD. This work provides novel insights into the role that different types of Aβ filaments may play in the composition of plaque morphology. Aggregation of Aβ as type Ic and type Id Aβ filaments may be the basis for the phenotype of CWPs. The characterization of Aβ filaments from CWPs, is important for the understanding of the role that the structure and assembly of amyloid peptides may play in the morphological diversity of Aβdeposits as well as for developing new diagnostic and therapeutic strategies for AD. (Supported by NIH P30-AG010133, RF1-NS110437and RF1-AG071177).
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APA 7th
Fernández, A., Hoq, M. R., Vago, F. S., Hallinan, G. I., Bharath, S., Li, D., et al. (2025). Cryo‐EM structures of amyloid β filaments from cotton wool plaques in Alzheimer disease caused by the PSEN1 V261I and A431E mutations. Alzheimer s & Dementia. https://doi.org/10.1002/alz70855_098033
Vancouver
Fernández A, Hoq MR, Vago FS, Hallinan GI, Bharath S, Li D, et al. Cryo‐EM structures of amyloid β filaments from cotton wool plaques in Alzheimer disease caused by the PSEN1 V261I and A431E mutations. Alzheimer s & Dementia. 2025. doi:10.1002/alz70855_098033. PMID: 41435289.
BibTeX
@article{fernandez2025-41435289,
author = {Fernández, Anllely and Hoq, Md Rejaul and Vago, Frank S. and Hallinan, Grace I. and Bharath, S.R. and Li, Daoyi and Ozcan, Kadir A. and Garringer, Holly J. and others},
title = {{Cryo‐EM structures of amyloid β filaments from cotton wool plaques in Alzheimer disease caused by the PSEN1 V261I and A431E mutations}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz70855_098033},
pmid = {41435289},
url = {https://doi.org/10.1002/alz70855_098033}
}
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Key findings
- CWPs consist predominantly of two novel arrangements of type I Aβ filaments, and we have designated them as type Ic and type Id Aβ filaments.
- The latter filaments exhibit unique protofilament packing arrangements.
- While the type Ic Aβ filaments share a largely similar S-shaped monomeric configuration with type I Aβ filaments, type Id Aβ filaments display an antiparallel and asymmetric packing, in contrast to the twofold parallel arrangement characteristic of type Ib and Ic Aβ filaments.
- The formation of type Ic and type Id Aβ filaments in CWPs may be linked to a distinct array of Aβ peptide species present in CWPs, differing from those found in core plaques in sporadic AD.
- This work provides novel insights into the role that different types of Aβ filaments may play in the composition of plaque morphology.
Why it matters
This structural study describes two new arrangements of amyloid-beta filaments found in cotton wool plaques from people with Alzheimer's disease caused by specific PSEN1 mutations. It may help scientists understand how plaque structure varies and could inform future diagnostic and therapeutic strategies, but it does not test any treatment or prevention.
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Study details
- Evidence strengthLow
How this study scored 31/100
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. We have no data on senior author's track record, so that was left out: it earned 30 of the 96 points we could judge it on, which is 31 out of 100.
| 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 | 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 | 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 | — / 4 | OpenAlex's profile for last-listed author Bernardino Ghetti holds only 4 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 1 / 3 | Purdue University West Lafayette: institution h-index 983 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41435289) |
| Free to read | 2 / 2 | Free to read |
| Points | 30 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 30 of the 96 points we could judge it on is 31 out of 100. |
| Total | 31 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1002/alz70855_098033
- PubMed: 41435289
- Original source →
- Free full text: Alzheimer s & Dementia →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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