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The development of methods to enrich cell\u2010specific EVs from biofluids has enabled us to monitor difficult\u2010to\u2010access organs, such as the brain, in real time without disrupting their function, thus serving as liquid biopsy. Burgeoning evidence indicates that the contents of neuron\u2010derived EVs (NDEs) in blood reveal dynamic alterations that occur during neurodegenerative pathogenesis, including Alzheimer's disease (AD), reflecting a disease\u2010specific molecular signature. Among these AD\u2010specific molecular changes is brain insulin\u2010signaling dysregulation, which cannot be assessed clinically in a living patient and remains an unexplained co\u2010occurrence during AD pathogenesis. This review is focused on delineating how NDEs in the blood may begin to close the gap between identifying molecular changes associated with brain insulin dysregulation reliably in living patients and its connection to AD. This approach could lead to the identification of novel early and less\u2010invasive diagnostic molecular biomarkers for AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Neuron\u2010derived extracellular vesicles (NDEs) could be isolated from peripheral blood.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>NDEs in blood reflect the molecular signature of Alzheimer's disease (AD).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Brain insulin\u2010signaling dysregulation plays a critical role in AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>NDEs in blood could predict brain insulin\u2010signaling dysregulation.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>NDEs offer novel early and less\u2010invasive diagnostic biomarkers for AD.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14497","type":"journal-article","created":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T08:30:23Z","timestamp":1737102623000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Neuron\u2010derived extracellular vesicles as a liquid biopsy for brain insulin dysregulation in Alzheimer's disease and related disorders"],"prefix":"10.1002","volume":"21","author":[{"given":"Jacob 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