Intranasal amniotic vesicles improved cognition in Alzheimer's mice and protected human neurons in vitro
In female 3×Tg-AD mice, intranasal extracellular vesicles from human amniotic membrane cells improved cognition and reduced neuroinflammation; they also protected human AD neurons in vitro.
Researchers from Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS and the E. Menni Research Center of Fondazione Poliambulanza reported in Translational Neurodegeneration that extracellular vesicles from human amniotic membrane mesenchymal stromal cells (hAMSC-EVs), given intranasally, improved cognition in female 3×Tg-AD mice biomedcentral.com
Translational Neurodegenerationbiomedcentral.comOpen source ↗. The paper is dated 9 September 2026. The animals received the vesicles chronically from 3 to 9 months of age.
Effects in the mouse model
Cognitive performance was assessed with novel object recognition, object place recognition and Y-maze tests. The authors report that the vesicles reached the hippocampus and were internalized by neurons and microglia. Treated mice performed significantly better, and hippocampal amyloid-β levels were lower, while tau phosphorylation was not affected.
The treatment also acted on neuroinflammation. Microglial and astrocytic density decreased, microglia showed structural remodeling, and expression of TMEM119 and TREM2 was downregulated. The cytokine profile shifted toward an anti-inflammatory one, and the hippocampus showed higher levels of the neuroplasticity-related proteins BDNF, GluA1 and ARC. Bioinformatic analysis of the vesicles' miRNA cargo identified enrichment in immunomodulatory and neuroprotective pathways.
Human neurons and study limits
To check relevance for humans, the team used glutamatergic neurons differentiated from induced pluripotent stem cells derived from patients with sporadic Alzheimer's disease. According to the publication's retelling, the source cells came from skin biopsies taken at the Policlinico's Memory Clinic. In these neurons the vesicles prevented neurite atrophy and rescued synaptic protein expression without affecting cell viability biomedcentral.com
Translational Neurodegenerationbiomedcentral.comOpen source ↗.
The authors conclude that hAMSC-EVs have anti-inflammatory and neuroprotective effects in both mouse and human cellular models, and describe intranasal delivery as a potential adjuvant strategy aimed at neuroinflammation and neurodegeneration. Professor Salvatore Fusco noted that research should look beyond the accumulation of beta-amyloid and tau to the cellular environment of neurons, including microglia and astrocytes, and the signals they exchange.
Professor Claudio Grassi stressed that these are preclinical results. They require further validation in humans and do not yet represent an available therapy for Alzheimer's disease.
