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Exosome-associated cargo is linked to familial Alzheimer's disease-associated phenotypes in vitro

Year: 2026

Type: article

Abstract: The propagation of pathological proteins such as tau and amyloid-beta (Aβ) in Alzheimer's disease (AD) is poorly understood. Here, we developed a human-relevant in vitro conditioned medium (CM)-based model using human neural progenitor ReN cells carrying Familial AD (FAD) mutations in amyloid precursor protein (APP Sw/Lo) and presenilin 1 (PSEN1ΔE9). Healthy ReN-derived neurons and astrocytes treated with FAD-CM for nine weeks exhibited AD features, including cellular toxicity, neuro-glial alterations, and mitochondrial dysfunction. Exogenous Aβ42 further induced neuroglial and mitochondrial damage. Exosomes released by FAD cells and -to a lesser extent- by CM-treated healthy cells showed elevated Aβ42/40 ratios. Proteomic analysis also revealed that exosomes from FAD-cells carried a distinct content, including overrepresentation of proteins linked to inflammation, extracellular matrix remodelling, synaptic dysfunction, and Aβ processing, as well as Calmodulin-like protein 3. Moreover, exosomes were actively internalized by healthy cells through an actin-dependent mechanism. In summary, these findings support a model based on FAD-associated APP/PSEN1 mutations in which exosome-associated cargo alongside soluble and non-vesicular factors contribute to the transfer of AD-associated cellular phenotypes.

Source: Disease Models & Mechanisms

DOI: 10.1242/dmm.052734

Authors: Zahra Motamed, Daniel Heutschi, Gaiser Carine, Laura Suter-Dick

Institutions: University of Basel, FHNW University of Applied Sciences and Arts Northwestern Switzerland, Swiss Centre for Applied Human Toxicology

Language: English

Topic: Alzheimer's disease research and treatments

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $3,750

OpenAlex ID: W7225648909

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