TY  - JOUR
AU  - Arbaciauskaite, Skaiste
AU  - Silvestri, Simona
AU  - Luo, Pingyan
AU  - Krüger, Christina
AU  - Mossmann, Zoe Julia
AU  - Allelein, Susann
AU  - Scholz, Alexander
AU  - Loeffler, Dennis
AU  - Fiorenza, Samuele
AU  - Menale, Anna
AU  - Torino, Enza
AU  - Kuhlmeier, Dirk
AU  - Peters, Oliver
AU  - Lehnardt, Seija
TI  - Microglia-Derived Extracellular Vesicles from Alzheimer's Disease Patients Carry miRNAs Driving a Neuroinflammatory Response.
JO  - Molecular neurobiology
VL  - 63
IS  - 1
SN  - 0893-7648
CY  - Totowa, NJ
PB  - Humana Press
M1  - DZNE-2026-00198
SP  - 435
PY  - 2026
AB  - 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.
KW  - Microglia: metabolism
KW  - Microglia: pathology
KW  - Alzheimer Disease: genetics
KW  - Alzheimer Disease: cerebrospinal fluid
KW  - Alzheimer Disease: pathology
KW  - Alzheimer Disease: metabolism
KW  - Extracellular Vesicles: metabolism
KW  - Humans
KW  - MicroRNAs: metabolism
KW  - MicroRNAs: genetics
KW  - Animals
KW  - Mice
KW  - Neuroinflammatory Diseases: genetics
KW  - Neuroinflammatory Diseases: pathology
KW  - Neuroinflammatory Diseases: metabolism
KW  - Aged
KW  - Male
KW  - Female
KW  - HEK293 Cells
KW  - Aged, 80 and over
KW  - Alzheimer’s disease (Other)
KW  - EV engineering (Other)
KW  - Extracellular vesicles (Other)
KW  - MicroRNA (Other)
KW  - Microglia (Other)
KW  - RNA delivery (Other)
KW  - Toll-like Receptors (Other)
KW  - MicroRNAs (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41678018
C2  - pmc:PMC12901236
DO  - DOI:10.1007/s12035-026-05719-w
UR  - https://pub.dzne.de/record/285256
ER  -