Phosphorylated tau in cerebrospinal fluid-derived extracellular vesicles in Alzheimer's disease: a pilot study.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Alzheimer Disease*/cerebrospinal fluid ; Alzheimer Disease*/metabolism ; Alzheimer Disease*/pathology ; Extracellular Vesicles*/metabolism ; tau Proteins*/cerebrospinal fluid ; tau Proteins*/metabolism; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Biomarkers/cerebrospinal fluid ; Phosphorylation ; Pilot Projects

Alzheimer's disease (AD) is a debilitating neurodegenerative disorder characterized by brain aggregation of β-amyloid (Aβ) peptides and phosphorylated tau (P-tau) proteins. Extracellular vesicles (EVs) can be isolated and studied for potential roles in disease. While several studies have tested plasma-derived EVs in AD, few have analyzed EVs from cerebrospinal fluid (CSF), which are potentially more closely related to brain changes. This study included 20 AD patients and 20 cognitively unimpaired (CU) participants. Using a novel EV isolation method based on acoustic trapping, we isolated and purified EVs from minimal CSF volumes. EVs were lysed and analyzed by immunoassays for P-tau217 and P-tau181. Isolation was confirmed through transmission electron microscopy and the presence of EV-specific markers (CD9, CD63, CD81, ATP1A3). Nanoparticle tracking analysis revealed a high variance in EV distribution. AD patients exhibited increased P-tau181 and decreased P-tau217 in EVs, leading to a higher EV P-tau181/P-tau217 ratio compared to CU. No significant differences in EV counts or sizes were observed between AD and CU groups. This study is the first to use acoustic trapping to isolate EVs from CSF and demonstrates differential P-tau content in AD-derived EVs, warranting further research to understand the relationship between these EV changes and brain pathology.
(© 2024. The Author(s).)

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Keywords: Acoustic trapping; Alzheimer’s disease; Biomarkers; Extracellular vesicles; P-tau181; P-tau217

0 (Biomarkers)
0 (tau Proteins)
0 (MAPT protein, human)

Date Created: 20241025 Date Completed: 20241025 Latest Revision: 20241031

20250114

PMC11511998

10.1038/s41598-024-75406-0

39455624