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Updated: Dec 26, 2025
Enrichment of Astrocyte-Derived Extracellular Vesicles from Human Plasma
Published on: August 3, 2022
Endothelial-derived plasma exosome proteins in Alzheimer's disease angiopathy
Erin L Abner1,2, Fanny M Elahi3, Gregory A Jicha1,4
1Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
Abstract:
Small cerebral vascular disease (SCeVD) demonstrated by white matter hyperintensity (WMH) on MRI contributes to the development of dementia in Alzheimer's disease (AD), but it has not been possible to correlate onset, severity, or protein components of SCeVD with characteristics of WMH in living patients. Plasma endothelial-derived exosomes (EDEs) were enriched by two-step immunoabsorption from four groups of participants with no clinical evidence of cerebrovascular disease: cognitively normal (CN) without WMH (CN without SCeVD, n = 20), CN with SCeVD (n = 22), preclinical AD (pAD) + mild cognitive impairment (MCI) without SCeVD (pAD/MCI without SCeVD, n = 22), and pAD/MCI with SCeVD (n = 16) for ELISA quantification of cargo proteins. Exosome marker CD81-normalized EDE levels of the cerebrovascular-selective biomarkers large neutral amino acid transporter 1 (LAT-1), glucose transporter type 1 (Glut-1), and permeability-glycoprotein (p-GP, ABCB1) were similarly significantly higher in the CN with SCeVD and pAD/MCI with SCeVD groups than their corresponding control groups without SCeVD. CD81-normalized EDE levels of Aβ40 and Aβ42 were significantly higher in the pAD/MCI with SCeVD group but not in the CN with SCeVD group relative to controls without SCeVD. Levels of normal cellular prion protein (PrPc), a receptor for amyloid peptides, and phospho-181T-tau were higher in both CN and pAD/MCI with SCeVD groups than in the corresponding controls. High EDE levels of Aβ40, Aβ42, and phospho-181T-tau in patients with WMH suggesting SCeVD appear at the pre-clinical or MCI stage of AD and therapeutic lowering of neurotoxic peptide levels may delay progression of AD angiopathy.
Insights
Small cerebral vascular disease (SCVD) is linked to Alzheimer's disease (AD) dementia. Elevated plasma endothelial-derived exosomes (EDEs) carrying specific proteins like Aβ40, Aβ42, and phospho-181T-tau indicate SCVD in early AD stages.
Area of Science:
- Neuroscience
- Biochemistry
- Medical Imaging
Background:
- Small cerebral vascular disease (SCVD), indicated by white matter hyperintensity (WMH) on MRI, contributes to Alzheimer's disease (AD) dementia.
- Current methods lack correlation between SCVD onset, severity, protein components, and WMH characteristics in living patients.
Purpose of the Study:
- To investigate the relationship between SCVD, WMH, and AD by analyzing protein cargo within plasma endothelial-derived exosomes (EDEs).
- To identify potential biomarkers for early detection and therapeutic targets in SCVD and AD.
Main Methods:
- Plasma EDEs were isolated from four participant groups: cognitively normal (CN) without SCVD, CN with SCVD, preclinical AD (pAD)/mild cognitive impairment (MCI) without SCVD, and pAD/MCI with SCVD.
- ELISA was used to quantify CD81-normalized EDE levels of cerebrovascular biomarkers (LAT-1, Glut-1, p-GP), amyloid-beta peptides (Aβ40, Aβ42), normal cellular prion protein (PrPc), and phospho-181T-tau.
Main Results:
- Significantly higher EDE levels of LAT-1, Glut-1, and p-GP were observed in participants with SCVD (both CN and pAD/MCI groups) compared to controls without SCVD.
- Elevated EDE levels of Aβ40, Aβ42, and phospho-181T-tau were found in the pAD/MCI with SCVD group, and phospho-181T-tau and PrPc were elevated in both SCVD groups.
- These findings suggest that SCVD-related protein changes in EDEs are present even at the preclinical or MCI stages of AD.
Conclusions:
- Elevated EDE levels of Aβ40, Aβ42, and phospho-181T-tau in patients with WMH indicative of SCVD appear at early AD stages.
- Targeting and reducing neurotoxic peptide levels may offer a therapeutic strategy to delay AD progression and vascular pathology.
