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Updated: Aug 21, 2025
Detecting Amyloid-β Accumulation via Immunofluorescent Staining in a Mouse Model of Alzheimer's Disease
Published on: April 19, 2021
Medin co-aggregates with vascular amyloid-β in Alzheimer's disease
Jessica Wagner1,2,3, Karoline Degenhardt1,2,3, Marleen Veit1,2,3
1German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Abstract:
Aggregates of medin amyloid (a fragment of the protein MFG-E8, also known as lactadherin) are found in the vasculature of almost all humans over 50 years of age1,2, making it the most common amyloid currently known. We recently reported that medin also aggregates in blood vessels of ageing wild-type mice, causing cerebrovascular dysfunction3. Here we demonstrate in amyloid-β precursor protein (APP) transgenic mice and in patients with Alzheimer's disease that medin co-localizes with vascular amyloid-β deposits, and that in mice, medin deficiency reduces vascular amyloid-β deposition by half. Moreover, in both the mouse and human brain, MFG-E8 is highly enriched in the vasculature and both MFG-E8 and medin levels increase with the severity of vascular amyloid-β burden. Additionally, analysing data from 566 individuals in the ROSMAP cohort, we find that patients with Alzheimer's disease have higher MFGE8 expression levels, which are attributable to vascular cells and are associated with increased measures of cognitive decline, independent of plaque and tau pathology. Mechanistically, we demonstrate that medin interacts directly with amyloid-β to promote its aggregation, as medin forms heterologous fibrils with amyloid-β, affects amyloid-β fibril structure, and cross-seeds amyloid-β aggregation both in vitro and in vivo. Thus, medin could be a therapeutic target for prevention of vascular damage and cognitive decline resulting from amyloid-β deposition in the blood vessels of the brain.
Insights
Medin amyloid, common in aging humans, worsens cerebrovascular dysfunction. Medin interacts with amyloid-beta, promoting its aggregation and potentially serving as a therapeutic target for cognitive decline.
Area of Science:
- Neuroscience
- Biochemistry
- Gerontology
Background:
- Medin amyloid aggregates are prevalent in the vasculature of aging individuals.
- Medin aggregation in blood vessels causes cerebrovascular dysfunction.
- Medin is a fragment of MFG-E8 (lactadherin).
Purpose of the Study:
- To investigate the relationship between medin and vascular amyloid-beta deposition in Alzheimer's disease.
- To determine the role of medin in promoting amyloid-beta aggregation.
- To explore medin as a potential therapeutic target for cognitive decline.
Main Methods:
- Studied amyloid precursor protein (APP) transgenic mice and Alzheimer's disease patients.
- Analyzed co-localization of medin and amyloid-beta in brain vasculature.
- Assessed the impact of medin deficiency on amyloid-beta deposition in mice.
- Measured MFG-E8 and medin levels in relation to vascular amyloid-beta burden.
- Analyzed ROSMAP cohort data for MFGE8 expression and cognitive decline.
- Investigated medin-amyloid-beta interactions in vitro and in vivo.
Main Results:
- Medin co-localizes with vascular amyloid-beta deposits in APP transgenic mice and Alzheimer's patients.
- Medin deficiency reduced vascular amyloid-beta deposition by 50% in mice.
- MFG-E8 and medin levels increase with vascular amyloid-beta burden severity.
- Higher MFGE8 expression in Alzheimer's patients correlates with cognitive decline, independent of plaque and tau.
- Medin directly interacts with amyloid-beta, promoting its aggregation and altering fibril structure.
Conclusions:
- Medin aggregation is closely linked to vascular amyloid-beta deposition and cognitive decline.
- Medin directly promotes amyloid-beta aggregation, forming heterologous fibrils.
- Medin represents a potential therapeutic target for preventing vascular damage and cognitive decline associated with amyloid-beta deposition.
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