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The coarse-grained plaque: a divergent Aβ plaque-type in early-onset Alzheimer's disease
Boon BDC, Bulk M, Jonker AJ, Morrema THJ, van den Berg E, Popovic M, Walter J, Kumar S et al.. Acta neuropathologica, 2020-09-14
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) deposits, which come in myriad morphologies with varying clinical relevance. Previously, we observed an atypical Aβ deposit, referred to as the coarse-grained plaque. In this study, we evaluate the plaque's association with clinical disease and perform in-depth immunohistochemical and morphological characterization. The coarse-grained plaque, a relatively large (Ø ≈ 80 µm) deposit, characterized as having multiple cores and Aβ-devoid pores, was prominent in the neocortex. The plaque was semi-quantitatively scored in the middle frontal gyrus of Aβ-positive cases (n = 74), including non-demented cases (n = 15), early-onset (EO)AD (n = 38), and late-onset (LO)AD cases (n = 21). The coarse-grained plaque was only observed in cases with clinical dementia and more frequently present in EOAD compared to LOAD. This plaque was associated with a homozygous APOE ε4 status and cerebral amyloid angiopathy (CAA). In-depth characterization was done by studying the coarse-grained plaque's neuritic component (pTau, APP, PrP C ), Aβ isoform composition (Aβ 40 , Aβ 42 , Aβ N3pE , pSer8Aβ), its neuroinflammatory component (C4b, CD68, MHC-II, GFAP), and its vascular attribution (laminin, collagen IV, norrin). The plaque was compared to the classic cored plaque, cotton wool plaque, and CAA. Similar to CAA but different from classic cored plaques, the coarse-grained plaque was predominantly composed of Aβ 40 . Furthermore, the coarse-grained plaque was distinctly associated with both intense neuroinflammation and vascular (capillary) pathology. Confocal laser scanning microscopy (CLSM) and 3D analysis revealed for most coarse-grained plaques a particular Aβ 40 shell structure and a direct relation with vessels. Based on its morphological and biochemical characteristics, we conclude that the coarse-grained plaque is a divergent Aβ plaque-type associated with EOAD. Differences in Aβ processing and aggregation, neuroinflammatory response, and vascular clearance may presumably underlie the difference between coarse-grained plaques and other Aβ deposits. Disentangling specific Aβ deposits between AD subgroups may be important in the search for disease-mechanistic-based therapies.
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APA 7th
Boon, B. D. C., Bulk, M., Jonker, A. J., Morrema, T. H. J., van den Berg, E., Popovic, M., et al. (2020). The coarse-grained plaque: a divergent Aβ plaque-type in early-onset Alzheimer's disease. Acta neuropathologica. https://doi.org/10.1007/s00401-020-02198-8
Vancouver
Boon BDC, Bulk M, Jonker AJ, Morrema THJ, van den Berg E, Popovic M, et al. The coarse-grained plaque: a divergent Aβ plaque-type in early-onset Alzheimer's disease. Acta neuropathologica. 2020. doi:10.1007/s00401-020-02198-8. PMID: 32926214.
BibTeX
@article{boon2020-32926214,
author = {Boon, B. D. C. and Bulk, M. and Jonker, A. J. and Morrema, T. H. J. and van den Berg, E. and Popovic, M. and Walter, J. and Kumar, S. and others},
title = {{The coarse-grained plaque: a divergent Aβ plaque-type in early-onset Alzheimer's disease}},
journal = {Acta neuropathologica},
year = {2020},
doi = {10.1007/s00401-020-02198-8},
pmid = {32926214},
url = {https://doi.org/10.1007/s00401-020-02198-8}
}
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Key findings
- Previously, we observed an atypical Aβ deposit, referred to as the coarse-grained plaque.
- The coarse-grained plaque was only observed in cases with clinical dementia and more frequently present in EOAD compared to LOAD.
- This plaque was associated with a homozygous APOE ε4 status and cerebral amyloid angiopathy (CAA).
- The plaque was compared to the classic cored plaque, cotton wool plaque, and CAA.
- Furthermore, the coarse-grained plaque was distinctly associated with both intense neuroinflammation and vascular (capillary) pathology.
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Study details
- Participants74
- Evidence strengthLow
How this study scored 52/100
Published in a leading specialty journal. Scored zero for study design, effect reported 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 and multi-centre collaboration, so those were left out: it earned 30 of the 58 points we could judge it on, which is 52 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Acta neuropathologica) |
| 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 | 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 | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 1 / 4 | 74 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 | — / 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 32926214) |
| Free to read | 2 / 2 | Free to read |
| Points | 30 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 30 of the 58 points we could judge it on is 52 out of 100. |
| Total | 52 / 100 | — |
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