Alzheimer’s disease (AD) remains a major neurodegenerative disorder lacking effective long-term disease-modifying therapies. Current pharmacological approaches provide primarily symptomatic benefit, while recently approved anti-amyloid monoclonal antibodies offer only modest clinical efficacy and are constrained by safety concerns, high costs, and limited blood–brain barrier (BBB) penetration. In this context, exosome-based strategies have emerged as potential therapeutic platforms in AD research. As endogenous nanovesicles, exosomes exhibit favorable biocompatibility, intrinsic BBB-crossing capacity, and the ability to deliver diverse therapeutic cargo across multiple pathological pathways. Through bioengineering approaches, exosomes may additionally be optimized for targeted brain delivery and therapeutic personalization. Nevertheless, despite their conceptual and preclinical advantages, exosome-based therapies remain at an early translational stage, with unresolved challenges related to large-scale production, standardization, biodistribution, and long-term safety. This review provides a comparative translational analysis of conventional and exosome-based therapeutic strategies in AD, focusing on mechanistic targeting, delivery efficiency, safety and tolerability, therapeutic personalization, and translational readiness. We critically evaluate the extent to which exosome-based platforms may address the limitations of current therapies while highlighting the key barriers that continue to limit their clinical translation and real-world applicability.
E. Andreadou, Evangelia Evangelopoulou, Magdalini Tsolaki et al.· Current Issues in Molecular...· 1 citation
Background/Objectives: Sleep disturbances are increasingly implicated in age-related cognitive decline and may contribute to heterogeneity in cognitive and social–cognitive functioning in Mild Cognitive Impairment (MCI). Nevertheless, it remains unclear whether longitudinal actigraphy-derived sleep parameters predict social cognition, including theory of mind (ToM), across amnestic (aMCI) and non-amnestic (naMCI) MCI subtypes. This study examined longitudinal trajectories of cognitive control and ToM in individuals with aMCI and naMCI and healthy older adults, and investigated whether actigraphy-derived sleep indices prospectively predict subsequent cognitive control and higher-order social cognition across these groups. Methods: A total of 179 participants (46 healthy controls, 75 aMCI, 58 naMCI) were assessed across three waves over approximately 16–20 months. Actigraphy-derived sleep indices were obtained using wrist actigraphy. Cognitive control was assessed with Delis–Kaplan Executive Function System subtests, whereas ToM was evaluated through tasks involving non-literal language comprehension, metaphor and proverb interpretation, higher-order mentalizing, and emotion recognition. Longitudinal trajectories were examined using mixed-design ANOVAs, and prospective sleep effects were tested using longitudinal path models. Results: Both cognitive control and ToM declined over time in the MCI groups, whereas healthy controls showed relative stability. Subtype differences in cognitive control emerged primarily in higher-order planning and rule-monitoring processes, with naMCI showing greater impairment. ToM revealed a clearer and more consistent gradient (healthy controls > aMCI > naMCI), particularly in higher-order inferential tasks. Among the actigraphy-derived sleep indices, only TST prospectively predicted later ToM performance, whereas prospective associations with cognitive control were limited and inconsistent. Conclusions: Reduced sleep duration was prospectively associated with poorer subsequent performance in higher-order social cognition, independently of the executive-control measures examined. These findings highlight phenotypic heterogeneity across MCI subtypes and suggest that objectively measured sleep duration may serve as a clinically relevant longitudinal marker of social–cognitive vulnerability. Future studies are needed to determine whether interventions targeting sleep duration are associated with improved social–cognitive outcomes.
A. Batzikosta, Magdalini Tsolaki, P. Steiropoulos et al.· Journal of Clinical Medicine· 0 citations
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