Journal Article

DZNE-2026-00198

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Microglia-Derived Extracellular Vesicles from Alzheimer's Disease Patients Carry miRNAs Driving a Neuroinflammatory Response.

Arbaciauskaite, S. ; Silvestri, S. ; Luo, P. ; Krüger, C. ; Mossmann, Z. J. ; Allelein, S. ; Scholz, A. ; Loeffler, D. ; Fiorenza, S. ; Menale, A. ; Torino, E. ; Kuhlmeier, D. ; Peters, O.DZNE* ; Lehnardt, S.

2026
Humana Press Totowa, NJ

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Please use a persistent id in citations: doi:10.1007/s12035-026-05719-w

Abstract: Alzheimer's disease (AD) represents the most common cause of dementia and urgently requires sensitive biomarkers and effective therapies. Extracellular vesicles represent membranous nano-sized particles secreted from cells, which serve as intercellular messengers participating in central nervous system (CNS) homeostasis, but also are implicated in AD pathogenesis. In addition, EVs containing disease-specific signatures, such as microRNAs (miRNAs), are considered as potent tools for the diagnosis and treatment of AD and other brain disorders. In this study, we used TMEM119 antibody to immunocapture microglia-derived EVs from cerebrospinal fluid (CSF) of AD patients and control subjects. EVs harvested from these CSF samples contained distinct disease-specific miRNA profiles, as assessed by small RNA sequencing. Using a HEK TLR reporter cell system, we found that these miRNA are potent activators of human TLR8, an established RNA sensor. Out of the miRNAs present in AD-associated EVs, selected oligonucleotides were synthesized and loaded into BV2 microglia-derived EVs. Exposure of primary murine microglia to these miRNA-loaded EVs led to TNF release from these cells, thereby driving a neuroinflammatory response. Taken together, putatively microglia-derived EVs from the CSF of AD patients contain miRNAs, which are capable of activating hTLR8 and inducing an inflammatory response from microglia.

Keyword(s): Microglia: metabolism (MeSH) ; Microglia: pathology (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Alzheimer Disease: cerebrospinal fluid (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Extracellular Vesicles: metabolism (MeSH) ; Humans (MeSH) ; MicroRNAs: metabolism (MeSH) ; MicroRNAs: genetics (MeSH) ; Animals (MeSH) ; Mice (MeSH) ; Neuroinflammatory Diseases: genetics (MeSH) ; Neuroinflammatory Diseases: pathology (MeSH) ; Neuroinflammatory Diseases: metabolism (MeSH) ; Aged (MeSH) ; Male (MeSH) ; Female (MeSH) ; HEK293 Cells (MeSH) ; Aged, 80 and over (MeSH) ; Alzheimer’s disease ; EV engineering ; Extracellular vesicles ; MicroRNA ; Microglia ; RNA delivery ; Toll-like Receptors ; MicroRNAs

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Contributing Institute(s):

1. Biomarker-Assisted Early Detection of Dementias (AG Peters)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DEAL Springer ; DEAL Springer ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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