Exosomes in Age-Related Cognitive Decline: Mechanistic Insights and Improving Outcomes

Abstract

Aging is the most prominent risk factor for cognitive decline, yet behavioral symptomology and underlying neurobiology can vary between individuals. Certain individuals exhibit significant age-related cognitive impairments, while others maintain intact cognitive functioning with only minimal decline. Recent developments in genomic, proteomic, and functional imaging approaches have provided insights into the molecular and cellular substrates of cognitive decline in age-related neuropathologies. Despite the emergence of novel tools, accurately and reliably predicting longitudinal cognitive trajectories and improving functional outcomes for the elderly remains a major challenge. One promising approach has been the use of exosomes, a subgroup of extracellular vesicles that regulate intercellular communication and are easily accessible compared to other approaches. In the current review, we highlight recent findings which illustrate how the analysis of exosomes can improve our understanding of the underlying neurobiological mechanisms that contribute to cognitive variation in aging. Specifically, we focus on exosome-mediated regulation of miRNAs, neuroinflammation, and aggregate-prone proteins. In addition, we discuss how exosomes might be used to enhance individual patient outcomes by serving as reliable biomarkers of cognitive decline and as nanocarriers to deliver therapeutic agents to the brain in neurodegenerative conditions.

Role of Exosomes in the Pathogenesis and Theranostic of Alzheimer’s Disease and Parkinson’s Disease

“…They facilitate the selective binding and uptake of exosomes, enabling the delivery of their “cargo” to specific cellular recipients. The presence of those receptors on exosomes facilitates their diagnostic application in NDDS [ 59 , 60 ]. Exosomes from patients with AD can be isolated from various biological fluids, including blood, urine, and saliva [ 60 ].…”

“…The presence of those receptors on exosomes facilitates their diagnostic application in NDDS [ 59 , 60 ]. Exosomes from patients with AD can be isolated from various biological fluids, including blood, urine, and saliva [ 60 ]. Hence, the non-invasive and convenient collection of exosomes, along with their stability after sample acquisition, further supports their utility in the field of diagnostics for AD and related disorders.…”

“…Exosomes derived from curcumin-treated cells inhibited the phosphorylation of Tau protein by activating the AKT/GSK-3β pathway, thereby preventing neuronal death both in vitro and in vivo and alleviating the symptoms of AD [ 74 ]. It has been reported that miRNA-193b present in exosomes derived from the serum, plasma, or CSF of healthy donors could bind to the 3′-UTR region of APP and suppress the expression of APP [ 60 ]. Vella et al reported that enzymes in exosomes such as neprilysin and insulin-degrading enzymes present in exosomes could degrade Aβ peptides and reduce extracellular and intracellular Aβ levels [ 75 ].…”

The rosetta stone of successful ageing: does oral health have a role?

“…Other forms of cell–cell communications are known to further drive the ageing process e.g. over gap junction mediated cell–cell contact with ROS (Salminen et al 2012 ) and exosome regulated communication (Nelson et al 2012 ; Duggan et al 2022 ; Xu and Tahara 2013 ). Altering intercellular communications will be an important target for potential interventions (Wang et al 2021a ; Piper et al 2011 ; Sanchez-Roman et al 2012 ; Loffredo et al 2013 ).…”

Therapeutic Strategy of Mesenchymal-Stem-Cell-Derived Extracellular Vesicles as Regenerative Medicine

“…Extracellular vesicles (EVs), which are nano- to micro-sized lipid bilayer membrane particles secreted by host cells, play critical roles in novel intercellular communication mechanisms, mediating the transduction of functional molecules with physiological activity, such as microRNAs, mRNAs, proteins, and lipids ( Figure 1 ) [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ,…”