Brain Region-specific Accumulation of Amyloidosis-associated Proteins in Postmortem Brain Tissues of Alzheimer’s Disease Patients Article Swipe
Wangchen Tsering
,
J. Philips
,
Todd E. Golde
,
Jonathan A. Villareal
,
Stefan Prokop
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-6649354/v1
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-6649354/v1
Numerous extracellular matrix (ECM) proteins, referred to as the matrisome, are increased in Alzheimer’s disease (AD). We recently demonstrated that many of these proteins colocalize with Aβ plaques and cerebral amyloid angiopathy (CAA), and some are present in dystrophic cellular processes within and around plaques. However, their precise roles in AD pathogenesis and their spatial and temporal distribution in postmortem brain tissue remain incompletely understood. Here, we performed a comprehensive immunohistochemistry analysis on postmortem brain samples spanning the spectrum of AD neuropathological change (ADNC: low, intermediate, and high). We assessed the accumulation of five matrisome proteins (MDK, SPOCK3, COL25aA1, SDC4, and EGFL8) across four brain regions differentially affected in AD (occipital cortex, hippocampus, striatum, and cerebellum), and examined their association with Aβ plaques, CAA, tau neurites, and neurofibrillary tangles (NFT). MDK in plaques increased consistently with ADNC severity across all regions. In contrast, SPOCK3, COL25A1, EGFL8, and SDC4 showed marked accumulation only in the occipital cortex and hippocampus, with sparse presence in the striatum and absence in the cerebellum. Notably, SPOCK3 exhibited pronounced regional specificity, with significantly higher levels in the hippocampus than in other areas. Patterns of plaque staining and degree of colocalization indicate that select matrisome proteins associate with either distinct types of Aβ deposits (e.g, fibrillar and neuritic versus diffuse plaques), while others may correlate more closely with tau pathology and/or dystrophic processes around plaques. Overall, our findings reveal region- and pathology-specific patterns of these matrisome protein accumulation during AD progression. These proteins represent intriguing biomarkers of AD and based on modeling studies represent potential therapeutic targets.
Related Topics
Concepts
Pathology
Colocalization
Senile plaques
Hippocampus
Biology
Alzheimer's disease
Cerebral amyloid angiopathy
Amyloid (mycology)
Cerebellum
Striatum
Neuroscience
Medicine
Disease
Dementia
Dopamine
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-6649354/v1
- https://www.researchsquare.com/article/rs-6649354/latest.pdf
- OA Status
- gold
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4410994787
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4410994787Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.21203/rs.3.rs-6649354/v1Digital Object Identifier
- Title
-
Brain Region-specific Accumulation of Amyloidosis-associated Proteins in Postmortem Brain Tissues of Alzheimer’s Disease PatientsWork title
- Type
-
preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-06-03Full publication date if available
- Authors
-
Wangchen Tsering, J. Philips, Todd E. Golde, Jonathan A. Villareal, Stefan ProkopList of authors in order
- Landing page
-
https://doi.org/10.21203/rs.3.rs-6649354/v1Publisher landing page
- PDF URL
-
https://www.researchsquare.com/article/rs-6649354/latest.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://www.researchsquare.com/article/rs-6649354/latest.pdfDirect OA link when available
- Concepts
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Pathology, Colocalization, Senile plaques, Hippocampus, Biology, Alzheimer's disease, Cerebral amyloid angiopathy, Amyloid (mycology), Cerebellum, Striatum, Neuroscience, Medicine, Disease, Dementia, DopamineTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- Related works (count)
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10Other works algorithmically related by OpenAlex
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