biostudies-literatureUnknown12(1)Badhwar A<h4>Introduction</h4>Brain cells secrete extracellular microvesicles (EVs) that cross the blood-brain barrier. Involved in cell-to-cell communication, EVs contain surface markers and a biologically active cargo of molecules specific to their tissue (and cell) of origin, reflecting the tissue or cell's physiological state. Isolation of brain-secreted EVs (BEVs) from blood provides a minimally invasive way to sample components of brain tissue in Alzheimer's disease (AD), and is considered a form of "liquid biopsy."<h4>Methods</h4>We performed a comprehensive review of the PubMed literature to assess the biomarker and therapeutic potential of blood-isolated BEVs in AD.<h4>Results</h4>We summarize methods used for BEV isolation, validation, and novel biomarker discovery, as well as provide insights from 26 studies in humans on the biomarker potential in AD of four cell-specific BEVs isolated from blood: neuron-, neural precursor-, astrocyte-, and brain vasculature-derived BEVs. Of these, neuron-derived BEVs has been investigated on several fronts, and these include levels of amyloid-β and tau proteins, as well as synaptic proteins. In addition, we provide a synopsis of the current landscape of BEV-based evaluation/monitoring of AD therapeutics based on two published trials and a review of registered clinical trials.<h4>Discussion</h4>Blood-isolated BEVs have emerged as a novel player in the study of AD, with enormous potential as a diagnostic, evaluation of therapeutics, and treatment tool. The literature has largely concentrated on neuron-derived BEVs in the blood in AD. Given the multifactorial pathophysiology of AD, additional studies, in neuron-derived and other brain cell-specific BEVs are warranted to establish BEVs as a robust blood-based biomarker of AD.Alzheimer's & dementia (Amsterdam, Netherlands)e12001https://www.ebi.ac.uk/biostudies/studies/S-EPMC7085285biostudies-literatureBiomarker potential of brain-secreted extracellular vesicles in blood in Alzheimer's disease.PMC7085285Haqqani ASBadhwar AfalseBiomarker potential of brain-secreted extracellular vesicles in blood in Alzheimer's disease.<h4>Introduction</h4>Brain cells secrete extracellular microvesicles (EVs) that cross the blood-brain barrier. Involved in cell-to-cell communication, EVs contain surface markers and a biologically active cargo of molecules specific to their tissue (and cell) of origin, reflecting the tissue or cell's physiological state. Isolation of brain-secreted EVs (BEVs) from blood provides a minimally invasive way to sample components of brain tissue in Alzheimer's disease (AD), and is considered a form of "liquid biopsy."<h4>Methods</h4>We performed a comprehensive review of the PubMed literature to assess the biomarker and therapeutic potential of blood-isolated BEVs in AD.<h4>Results</h4>We summarize methods used for BEV isolation, validation, and novel biomarker discovery, as well as provide insights from 26 studies in humans on the biomarker potential in AD of four cell-specific BEVs isolated from blood: neuron-, neural precursor-, astrocyte-, and brain vasculature-derived BEVs. Of these, neuron-derived BEVs has been investigated on several fronts, and these include levels of amyloid-β and tau proteins, as well as synaptic proteins. In addition, we provide a synopsis of the current landscape of BEV-based evaluation/monitoring of AD therapeutics based on two published trials and a review of registered clinical trials.<h4>Discussion</h4>Blood-isolated BEVs have emerged as a novel player in the study of AD, with enormous potential as a diagnostic, evaluation of therapeutics, and treatment tool. The literature has largely concentrated on neuron-derived BEVs in the blood in AD. Given the multifactorial pathophysiology of AD, additional studies, in neuron-derived and other brain cell-specific BEVs are warranted to establish BEVs as a robust blood-based biomarker of AD.2020-01-01T00:00:00Z20202025-04-18T21:15:13.926Z2025-04-07T09:12:11.348ZS-EPMC70852853221149710.1002/dad2.12001