Neurovascular Uncoupling in Alzheimer's and Parkinson's Diseases: Mechanisms and Therapeutic Strategies

Authors

• Akash Ved, Dr. APJ Abdul Kalam Technical University, Uttar Pradesh, India
• Tushar B. Gajjar, Gokul Global University, Gujarat, India
• Ashish Kakkad, Marwadi University Research Center, Gujarat, India
• Subbulakshmi Ganesan, JAIN (Deemed to be University), Karnataka, India
• Aman Shankhyan, Chitkara University, Punjab, India
• Karthikeyan Jayabalan, Sathyabama Institute of Science and Technology, Tamil Nadu, India
• Swati Mishra, IMS and SUM Hospital, Odisha, India
• Bhavik Jain, Sharda University, Uttar Pradesh, India
• Vimal Arora, Chandigarh University, Punjab, India
• Monica Gulati, Lovely Professional University, Punjab, India
• Tapan Behl, Amity University Punjab, Punjab, India
• Ansab Akhtar, LSU Health Sciences Center - New OrleansFollow

Document Type

Article

Publication Date

4-22-2026

Publication Title

Brain Sciences

Abstract

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's disease (AD) NVU is caused by Aβ buildup, tau pathology, endothelial dysfunction, and persistent neuroinflammation, leading to poor CBF control and blood-brain barrier (BBB) disintegration. Parkinson's disease (PD) is characterised by α-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 Aβ and α-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.

PubMed ID

42192747

Volume

16

Issue

5

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Ved, Akash; Gajjar, Tushar B.; Kakkad, Ashish; Ganesan, Subbulakshmi; Shankhyan, Aman; Jayabalan, Karthikeyan; Mishra, Swati; Jain, Bhavik; Arora, Vimal; Gulati, Monica; Behl, Tapan; and Akhtar, Ansab, "Neurovascular Uncoupling in Alzheimer's and Parkinson's Diseases: Mechanisms and Therapeutic Strategies" (2026). School of Graduate Studies Faculty Publications. 593.
https://digitalscholar.lsuhsc.edu/sogs_facpubs/593
10.3390/brainsci16050434