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@ARTICLE{Arbaciauskaite:285256,
author = {Arbaciauskaite, Skaiste and Silvestri, Simona and Luo,
Pingyan and Krüger, Christina and Mossmann, Zoe Julia and
Allelein, Susann and Scholz, Alexander and Loeffler, Dennis
and Fiorenza, Samuele and Menale, Anna and Torino, Enza and
Kuhlmeier, Dirk and Peters, Oliver and Lehnardt, Seija},
title = {{M}icroglia-{D}erived {E}xtracellular {V}esicles from
{A}lzheimer's {D}isease {P}atients {C}arry mi{RNA}s
{D}riving a {N}euroinflammatory {R}esponse.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
issn = {0893-7648},
address = {Totowa, NJ},
publisher = {Humana Press},
reportid = {DZNE-2026-00198},
pages = {435},
year = {2026},
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.},
keywords = {Microglia: metabolism / Microglia: pathology / Alzheimer
Disease: genetics / Alzheimer Disease: cerebrospinal fluid /
Alzheimer Disease: pathology / Alzheimer Disease: metabolism
/ Extracellular Vesicles: metabolism / Humans / MicroRNAs:
metabolism / MicroRNAs: genetics / Animals / Mice /
Neuroinflammatory Diseases: genetics / Neuroinflammatory
Diseases: pathology / Neuroinflammatory Diseases: metabolism
/ Aged / Male / Female / HEK293 Cells / Aged, 80 and over /
Alzheimer’s disease (Other) / EV engineering (Other) /
Extracellular vesicles (Other) / MicroRNA (Other) /
Microglia (Other) / RNA delivery (Other) / Toll-like
Receptors (Other) / MicroRNAs (NLM Chemicals)},
cin = {AG Peters},
ddc = {570},
cid = {I:(DE-2719)5000000},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41678018},
pmc = {pmc:PMC12901236},
doi = {10.1007/s12035-026-05719-w},
url = {https://pub.dzne.de/record/285256},
}