Profiling of microglial-originated microvesicles to unearthing their lurking potential as potent foreseeable biomarkers for the diagnosis of Alzheimer’s disease: A systematic review
Sri Harsha Kanuri, Prapthi Jayesh Sirrkay
Abstract
BACKGROUND: Alzheimer's Disease is a neurodegenerative disease characterized by accumulation of phosphorylated tau and amyloid deposits within the brain tissues in the elderly population. Numerous studies established that amassment of these toxic accretions within the brain tissues initiates neuronal demise and synaptic impairment which becomes the underlying basis for memory loss and cognitive abnormalities in these patients. HYPOTHESIS: Hypoxia, oxidative stress, and inflammation are commonly encountered perils in the neuronal milieu that derail the neuron-synapse interactions and maneuver them to undergo apoptosis. A spinoff from neuronal desecration is microglial activation which forms a cardinal role in mounting innate immune defenses for warding off and reversing off toxic stimulus encountered. RESULTS: A potential ramification of microglial activation in this context is assembly, processing and exuding of micro-vesicles into the extracellular space. These micro-vesicles will be packaged with amyloid and tau deposits which accumulate intracellularly within microglial cells secondary to their professional scavenging function. These microglial MVs are prone to seed tau and amyloid beta into the surrounding neuron-synapse framework, thus are implicated in spreading the disease pathology in AD. CONCLUSIONS: Therefore, these MVs can be considered as an omen for disease initiation, progression, monitoring as well gauging the treatment response in the clinical AD cohorts. We speculate future research studies to unmask the dormant potential of these microglial MVs as reliable markers for diagnosis, evaluating the disease progression as well as treatment in AD. This will open the door for early diagnosis of AD so as to prioritize management and optimize clinical outcomes..