Evidence map›Paper›PMID 41923110›Full record

ArticleAlzheimer's research & therapy2026

Intranasal administration of neural stem cell-derived extracellular vesicles prevents cognitive decline in both male and female 3×Tg-AD mice by dampening neuroinflammation and epigenetically regulating amyloid β metabolism.

Francesca Natale, Alice Dellaria, Ida Nifo Sarrapochiello, Lucia Leone, Matteo Spinelli, Marco Rinaudo, Nicoletta Garofalo, Claudio Grassi, Salvatore Fusco

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Article in Alzheimer's research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Francesca Natale *Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, 00168, Italy.
Alice Dellaria *Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, 00168, Italy.
Ida Nifo SarrapochielloDepartment of Neuroscience, Università Cattolica del Sacro Cuore, Rome, 00168, Italy.
Lucia LeoneDepartment of Neuroscience, Università Cattolica del Sacro Cuore, Rome, 00168, Italy.
Matteo SpinelliDepartment of Neuroscience, Università Cattolica del Sacro Cuore, Rome, 00168, Italy.
Marco RinaudoDepartment of Neuroscience, Università Cattolica del Sacro Cuore, Rome, 00168, Italy.
Nicoletta GarofaloDepartment of Neuroscience, Università Cattolica del Sacro Cuore, Rome, 00168, Italy.
Claudio GrassiDepartment of Neuroscience, Università Cattolica del Sacro Cuore, Rome, 00168, Italy. claudio.grassi@unicatt.it.
Salvatore FuscoDepartment of Neuroscience, Università Cattolica del Sacro Cuore, Rome, 00168, Italy.

Funding

Ministero della Salute Ricerca Corrente
6 · The paper itself

Abstract

backgroundAlzheimer’s disease (AD) is the leading cause of dementia in the elderly and poses a significant socioeconomic burden due to its progressive nature and lack of effective treatments. Recent studies suggest that neural stem cell-derived extracellular vesicles (NSC-EV) hold therapeutic potential against AD by delivering bioactive molecules that counteract neuroinflammation, oxidative stress, and protein dysregulation.

methodsNSC-EV were intranasally administered to both male and female 3×Tg-AD mice from three to twelve months of age and cognitive function were evaluated at multiple time points. Moreover, neuroinflammation and amyloid-β (Aβ) metabolism markers were studied at 9 months of age.

resultsIntranasal administration of NSC-EV delayed cognitive decline, reduced hippocampal neuroinflammation, and decreased Aβ accumulation in both male and female 3×Tg-AD mice. These functional effects were accompanied by the downregulation of STAT5 expression, which is a mediator of neuroinflammatory signaling, and the upregulation of neuroprotective transcription factor NRF2. Moreover, the changes in STAT5 and NRF2 expression caused the epigenetic inhibition of pro-amyloidogenic beta secretase BACE1 transcription and the enhanced expression of IDE, which is the main enzyme involved in Aβ clearance. These events were accompanied by the reduction of Aβ levels.

conclusionsOur findings provide new insights into the molecular mechanisms by which NSC-EV modulate AD pathology and support their potential as a regenerative therapy for neurodegenerative diseases.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesCognitive DysfunctionEpigenesis, GeneticExtracellular VesiclesNeural Stem CellsNeuroinflammatory DiseasesAdministration, IntranasalAnimalsDisease Models, AnimalFemaleMaleMiceMice, TransgenicAmyloid beta-PeptidesAlzheimer’s diseaseamyloid-βBACE1EpigeneticsExtracellular vesiclesInsulin-degrading enzymeNeural stem cellsNeuroinflammation

Identifiers

PMID41923110
PMCPMC13188268

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.