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Variability in the type and layer distribution of cortical Aβ pathology in familial Alzheimer's disease
Nanet Willumsen, Teresa Poole, Jennifer M Nicholas, Nick C Fox, Natalie S Ryan, Tammaryn Lashley. Brain pathology (Zurich, Switzerland), 2021-07-28
Topic: Genetics and APOE
Familial Alzheimer's disease (FAD) is caused by autosomal dominant mutations in the PSEN1, PSEN2 or APP genes, giving rise to considerable clinical and pathological heterogeneity in FAD. Here we investigate variability in clinical data and the type and distribution of Aβ pathologies throughout the cortical layers of different FAD mutation cases. Brain tissue from 20 FAD cases [PSEN1 pre-codon 200 (n = 10), PSEN1 post-codon 200 (n = 6), APP (n = 4)] were investigated. Frontal cortex sections were stained immunohistochemically for Aβ, and Nissl to define the cortical layers. The frequency of different amyloid-beta plaque types was graded for each cortical layer and the severity of cerebral amyloid angiopathy (CAA) was determined in cortical and leptomeningeal blood vessels. Comparisons were made between FAD mutations and APOE4 status, with associations between pathology, clinical and genetic data investigated. In this cohort, possession of an APOE4 allele was associated with increased disease duration but not with age at onset, after adjusting for mutation sub-group and sex. We found Aβ pathology to be heterogeneous between cases although Aβ load was highest in cortical layer 3 for all mutation groups and a higher Aβ load was associated with APOE4. The PSEN1 post-codon 200 group had a higher Aβ load in lower cortical layers, with a small number of this group having increased cotton wool plaque pathology in lower layers. Cotton wool plaque frequency was positively associated with the severity of CAA in the whole cohort and in the PSEN1 post-codon 200 group. Carriers of the same PSEN1 mutation can have differing patterns of Aβ deposition, potentially because of differences in risk factors. Our results highlight possible influences of APOE4 genotype, and PSEN1 mutation type on Aβ deposition, which may have effects on the clinical heterogeneity of FAD.
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APA 7th
Willumsen, N., Poole, T., Nicholas, J. M., Fox, N. C., Ryan, N. S., & Lashley, T. (2022). Variability in the type and layer distribution of cortical Aβ pathology in familial Alzheimer's disease. Brain pathology (Zurich, Switzerland). https://doi.org/10.1111/bpa.13009
Vancouver
Willumsen N, Poole T, Nicholas JM, Fox NC, Ryan NS, Lashley T. Variability in the type and layer distribution of cortical Aβ pathology in familial Alzheimer's disease. Brain pathology (Zurich, Switzerland). 2022. doi:10.1111/bpa.13009. PMID: 34319632.
BibTeX
@article{willumsen2022-34319632,
author = {Willumsen, Nanet and Poole, Teresa and Nicholas, Jennifer M and Fox, Nick C and Ryan, Natalie S and Lashley, Tammaryn},
title = {{Variability in the type and layer distribution of cortical Aβ pathology in familial Alzheimer's disease}},
journal = {Brain pathology (Zurich, Switzerland)},
year = {2022},
doi = {10.1111/bpa.13009},
pmid = {34319632},
url = {https://doi.org/10.1111/bpa.13009}
}
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Key findings
- In this cohort, possession of an APOE4 allele was associated with increased disease duration but not with age at onset, after adjusting for mutation sub-group and sex.
- We found Aβ pathology to be heterogeneous between cases although Aβ load was highest in cortical layer 3 for all mutation groups and a higher Aβ load was associated with APOE4.
- Cotton wool plaque frequency was positively associated with the severity of CAA in the whole cohort and in the PSEN1 post-codon 200 group.
- Our results highlight possible influences of APOE4 genotype, and PSEN1 mutation type on Aβ deposition, which may have effects on the clinical heterogeneity of FAD.
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Study details
- Evidence strengthModerate
How this study scored 45/100
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. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 25 of the 56 points we could judge it on, which is 45 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Brain pathology (Zurich, Switzerland)) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 3 / 5 | 2022 — within 6 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34319632) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 25 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 25 of the 56 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | — |
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