An In Vivo C57BL/6 Mouse Study Demonstrating Fine-Tuning of Serum and Brain-Derived Exosomes Reveal Therapeutic Potential of Phytochemical Ferulic Acid Against Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by memory loss, synaptic impairment, and biochemical changes. The study aimed to investigate the neuroprotective role of ferulic acid (FA) in an AD mouse C57BL/6 model induced by the Aβ(25-35) peptide. Cognitive deficits, which include memory and spatial learning deficits caused by Aβ, were evaluated using a set of behavioural tests. Transmission electron microscopy (TEM), dynamic light scattering (DLS), and Western blot analysis were used to characterize the exosomes from the brain and the serum. The activity of acetylcholinesterase (AChE) in exosomes was also evaluated, and the proteomic analysis of the serum-derived exosomes was conducted through LC-MS Triple ToF and bioinformatics to identify the altered pathways associated with identified proteins. The results obtained showed that there were significant alterations in the exosomal proteome profile after Aβ treatment. The levels of some of the proteins that are involved in energy metabolism, amyloid clearance, cytoskeleton, oxidative stress, and neuroinflammation were particularly affected. Treatment with the phytochemical FA modulated the exosomal proteome profile alterations and the activity of AChE in exosomes, which are some of the hallmarks of cholinergic dysfunction in the case of AD. However, the analysis of the proteome of the AD condition revealed that there were distinct alterations in the content of serum-derived exosomes, which could be used as candidates for non-invasive biomarkers of AD progression. This work also highlights the possibility of using the phytochemical FA to prevent and treat the neurotoxicity and neurodegenerative cascade induced by Aβ and to correct the protein content of exosomes in AD.