Open Access

REVIEW

Interaction of Cellular and Molecular Mechanisms in Diabetes-Associated Neurodegeneration and Alzheimer’s Disease

Dominick Shoha^#, David Lei^#, Tyler Truong, Sophia Strukel, Elliot Enshaie, Vikrant Rai^*

Department of Translational Research, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, USA

* Corresponding Author: Vikrant Rai. Email:
# These authors contributed equally to this work

(This article belongs to the Special Issue: Unraveling the Interplay of Molecular and Cellular Mechanisms between Diabetes and Non-communicable Diseases )

BIOCELL 2026, 50(8), 6 https://doi.org/10.32604/biocell.2026.078846

Received 09 January 2026; Accepted 18 March 2026; Issue published 27 July 2026

Abstract

Diabetes, inflammation, and neurodegeneration, particularly Alzheimer’s disease (AD), are deeply interconnected (brain diabetes). Type 2 diabetes mellitus (T2DM) acts as a significant risk factor for neurodegenerative diseases like Alzheimer’s (AD) and Parkinson’s (PD) by inducing chronic inflammation, oxidative stress, and metabolic dysfunction. Hyperglycemia drives neuroinflammation and damages the blood-brain barrier (BBB), exacerbating cognitive decline and neuronal loss. Chronic inflammation acts as a central bridge, linking high blood sugar, insulin resistance, and metabolic dysfunction in the brain to the buildup of amyloid plaques, tau tangles, and neuronal damage due to shared insulin signaling issues in the brain. Diabetes accelerate AD risk through inflammation-driven mitochondrial damage and impaired insulin pathways, which hinder amyloid clearance and disrupt normal brain function. Insulin resistance and impaired glucose metabolism accelerate brain aging and neurodegeneration. This narrative review aims to summarize the underlying molecular and cellular mechanisms in the pathophysiology of hyperglycemia-associated neurodegeneration with a focus on Alzheimer’s disease as a manifestation of type 3 diabetes mellitus (type 2 diabetes in the brain).

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Keywords

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