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There is growing interest in the role of VEGF signalling in the pathophysiology of Alzheimer's disease (AD). The generation of single\u2010cell brain atlases and recent large multi\u2010omic studies, including analysis of CSF and bloods alongside post\u2010mortem brain tissue, have provided novel insights into the role of VEGF signalling in AD. Disruption of the VEGF\u2010A\/VEGFR2 signalling pathway, due in part to elevated soluble VEGFR1 expression may contribute to pathogenic angiogenesis, BBB leakiness, and neuronal loss in AD. Induction of VEGF\u2010B\/VEGFR1 signalling in microglia suggests that dysregulated VEGF\u2010mediated immune cell signalling is a further influence on AD pathogenesis. A reduction in expression of the \u2018protective\u2019 VEGFR3 and co\u2010receptors neuropilin 1 and 2 has also been recently linked to cognitive decline in AD. In large clinical studies, lower VEGF\u2010A levels in CSF and serum, raised soluble VEGFR1in CSF and elevated PlGF in CSF and serum, are predictive of more rapid cognitive decline and accelerated Alzheimer's disease neuropathological change (ADNC). This review discusses findings from recent multi\u2010omic studies of large clinical and neuropathological studies that prompt reconsideration of the nature of VEGF signalling in AD and shed light on some of the complexities and previous conflicts within the field.<\/jats:p>","DOI":"10.1111\/bpa.70100","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:50:31Z","timestamp":1776041431000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["New perspectives on\n                    <scp>VEGF<\/scp>\n                    signalling in Alzheimer's disease"],"prefix":"10.1111","volume":"36","author":[{"given":"Cherelle E. 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