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Cited by 77Alzheimer's disease research and treatmentsSpectroscopy Techniques in Biomedical and Chemical ResearchDementia and Cognitive Impairment Research

Label-free vibrational imaging of different Aβ plaque types in Alzheimer’s disease reveals sequential events in plaque development

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Röhr, Dominik, Boon, Baayla D. C., Schuler, Martin, Kremer, Kristin, Hoozemans, Jeroen J. M., Bouwman, Femke H., El-Mashtoly, Samir F., Nabers, Andreas +3 more·2020·Acta Neuropathologica Communications
DOI 10.1186/s40478-020-01091-5PMC PMC7733282
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Abstract

The neuropathology of Alzheimer’s disease (AD) is characterized by hyperphosphorylated tau neurofibrillary tangles (NFTs) and amyloid-beta (Aβ) plaques. Aβ plaques are hypothesized to follow a development sequence starting with diffuse plaques, which evolve into more compact plaques and finally mature into the classic cored plaque type. A better molecular understanding of Aβ pathology is crucial, as the role of Aβ plaques in AD pathogenesis is under debate. Here, we studied the deposition and fibrillation of Aβ in different plaque types with label-free infrared and Raman imaging. Fourier-transform infrared (FTIR) and Raman imaging was performed on native snap-frozen brain tissue sections from AD cases and non-demented control cases. Subsequently, the scanned tissue was stained against Aβ and annotated for the different plaque types by an AD neuropathology expert. In total, 160 plaques (68 diffuse, 32 compact, and 60 classic cored plaques) were imaged with FTIR and the results of selected plaques were verified with Raman imaging. In diffuse plaques, we detect evidence of short antiparallel β-sheets, suggesting the presence of Aβ oligomers. Aβ fibrillation significantly increases alongside the proposed plaque development sequence. In classic cored plaques, we spatially resolve cores containing predominantly large parallel β-sheets, indicating Aβ fibrils. Combining label-free vibrational imaging and immunohistochemistry on brain tissue samples of AD and non-demented cases provides novel insight into the spatial distribution of the Aβ conformations in different plaque types. This way, we reconstruct the development process of Aβ plaques in human brain tissue, provide insight into Aβ fibrillation in the brain, and support the plaque development hypothesis.

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  • Progressive deposits of Aβ fibrils into plaques create a positive feedback loop between inflammation and APP processing.

    “The progressive deposits of Aβ fibrils into plaques create a positive feedback loop between inflammation and APP processing [13].”

    From Microglia specific deletion of miR-155 in Alzheimer’s disease mouse models reduces amyloid-β pathology but causes hyperexcitability and seizures (2023) · cites this paper as [13]

    The Introduction (page unavailable) says Aβ aggregation induces an inflammatory response and that microglia-driven inflammation is considered to contribute to continued amyloid-fibril build-up. The Abstract and Discussion (pages unavailable) describe increasing fibrillation during plaque development. But the paper does not say that inflammation feeds back into APP processing, so it does not support the full proposed loop. (LLM, conf=0.86)

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Authors
Röhr, D., Boon, B. D. C., Schuler, M., Kremer, K., Hoozemans, J. J. M., Bouwman, F. H., El-Mashtoly, S. F., Nabers, A., Großerueschkamp, F., Rozemuller, A. J. M., & Gerwert, K.
Affiliations
  • Ruhr University Bochum (DE)
  • Amsterdam Neuroscience (NL)
Corresponding author
Gerwert, Klaus
ORCID
Venue
Acta Neuropathologica Communications
Publisher
Springer Science and Business Media LLC
Published
2020-12
Volume
8
Issue
1
Pages
222-222
ISSN
2051-5960 (ISSN-L)
DOI
10.1186/s40478-020-01091-5
PMC
PMC7733282
OpenAlex
W3113097844
Cited by
77
References
9
Citations by year
2026: 6 · 2025: 18 · 2024: 16 · 2023: 11 · 2022: 16 · 2021: 10
FWCI
5.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Neuropathologica Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion, other-oa)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders
  • Ministerium für Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen (233-1.08.03.03-031-68079)
  • Ministeriums für Kultur und Wissenschaft (111.08.03.05-133974)
  • Alzheimer Nederland (WE.15-2019-13)
  • ZonMw (733050104)
  • NIH (1R01AG061775)
  • Projekt DEAL
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Spectroscopy Techniques in Biomedical and Chemical Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, amyloid plaques, plaque development, diffuse plaques, amyloid fibril formation, antiparallel beta-sheet, parallel beta-sheet, FTIR imaging, Raman imaging, brain tissue
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Female, Humans, Male, Spectrum Analysis, Raman, Amyloid beta-Peptides, Spectroscopy, Fourier Transform Infrared, Disease Progression, Plaque, Amyloid

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