{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T21:48:38Z","timestamp":1792532918655,"version":"4.5.0"},"reference-count":194,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Neurovascular coupling (NVC) maintains appropriate cerebral blood flow (CBF) in response to neuronal activity, and its disturbance, known as neurovascular uncoupling (NVU), is increasingly recognised as a major contributor to neurodegenerative disease. Alzheimer\u2019s disease (AD) NVU is caused by A\u03b2 buildup, tau pathology, endothelial dysfunction, and persistent neuroinflammation, leading to poor CBF control and blood\u2013brain barrier (BBB) disintegration. Parkinson\u2019s disease (PD) is characterised by \u03b1-synuclein aggregation, oxidative stress, mitochondrial dysfunction, and dopaminergic neuronal loss, all of which impede cerebrovascular regulation. These disease-specific mechanisms interact via similar vascular pathways, establishing NVU as a critical connection between neuronal degeneration and cerebrovascular dysfunction. This study highlights the critical role of NVU in neurodegeneration by investigating shared and disease-specific processes in AD and PD. Tau pathology disturbs vascular regulation in AD, whereas dopaminergic neuron loss impairs cerebrovascular control in PD. Both A\u03b2 and \u03b1-synuclein are linked to endothelial dysfunction and oxidative stress, albeit originating in different pathologies. Comparative analysis reveals distinct vascular abnormalities in each condition, as well as shared processes such as inflammation and BBB disruption. The study also covers developments in biomarker discovery and neuroimaging techniques that allow for exact characterisation of NVU, facilitating early diagnosis and treatments. In addition, lifestyle changes and pharmacological treatments for oxidative stress and endothelial injury are being examined. This study highlights the significance of NVU as a fundamental pathogenic mechanism, underscoring its importance for comprehending disease development and formulating novel therapeutic strategies.<\/jats:p>","DOI":"10.3390\/brainsci16050434","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T09:01:24Z","timestamp":1776848484000},"page":"434","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Neurovascular Uncoupling in Alzheimer\u2019s and Parkinson\u2019s Diseases: Mechanisms and Therapeutic Strategies"],"prefix":"10.3390","volume":"16","author":[{"given":"Akash","family":"Ved","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, Dr. APJ Abdul Kalam Technical University, Lucknow 226031, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tushar B.","family":"Gajjar","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Gokul Global University, Sidhpur 384151, Gujarat, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish","family":"Kakkad","sequence":"additional","affiliation":[{"name":"Marwadi University Research Center, Department of Physiotherapy, Faculty of Health Sciences, Marwadi University, Rajkot 360003, Gujarat, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subbulakshmi","family":"Ganesan","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore 560041, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aman","family":"Shankhyan","sequence":"additional","affiliation":[{"name":"Centre for Research Impact & Outcome, Institute of Engineering and Technology, Chitkara University, Rajpura 140401, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthikeyan","family":"Jayabalan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Sathyabama Institute of Science and Technology, Chennai 600119, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati","family":"Mishra","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, IMS and SUM Hospital, Siksha \u2018O\u2019 Anusandhan (Deemed to be University), Bhubaneswar 751003, Odisha, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhavik","family":"Jain","sequence":"additional","affiliation":[{"name":"Sharda School of Pharmacy, Sharda University, Greater Noida 201310, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vimal","family":"Arora","sequence":"additional","affiliation":[{"name":"University Institute of Pharmacy Sciences, Chandigarh University, Mohali 140413, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Gulati","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, Punjab, India"},{"name":"Australian Research Centre in Complementary and Integrative Medicine (ARCCIM), Faculty of Health, University of Technology Sydney, Ultimo, NSW 2007, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tapan","family":"Behl","sequence":"additional","affiliation":[{"name":"Amity Institute of Pharmacy, Amity University Punjab, Mohali 140306, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4839-4454","authenticated-orcid":false,"given":"Ansab","family":"Akhtar","sequence":"additional","affiliation":[{"name":"LSU Health Sciences Center, School of Medicine, LSU Health New Orleans, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105983","DOI":"10.1016\/j.biocel.2021.105983","article-title":"Endothelial Signaling at the Core of Neurovascular Coupling: The Emerging Role of Endothelial Inward-Rectifier K+ (Kir2.1) Channels and N-Methyl-d-Aspartate Receptors in the Regulation of Cerebral Blood Flow","volume":"135","author":"Negri","year":"2021","journal-title":"Int. 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