Navigating the intersection: Diabetes and Alzheimer's intertwined relationship

Area of Science:

• Neuroscience
• Endocrinology
• Genetics

Background:

• Alzheimer's disease (AD) and Diabetes mellitus (DM) share overlapping pathophysiological pathways.
• Genetic factors like APP, PS-1, and PS-2 mutations are implicated in AD.
• Insulin resistance and dysfunction, termed 'type 3 diabetes mellitus,' are increasingly recognized in AD.

Purpose of the Study:

• To explore the interconnected mechanisms between Alzheimer's disease and Diabetes mellitus.
• To highlight shared pathways that could be targeted for therapeutic intervention.

Main Methods:

• Review of genetic abnormalities (APP, PS-1, PS-2) and biomarkers (CSF, blood) in AD.
• Analysis of insulin signaling pathways and their role in neurotoxicity and amyloid production.
• Examination of impaired glucose transporter expression, mitochondrial dysfunction, and inflammation (TLR4).

Main Results:

• Insulin dysfunction in AD affects insulin signaling and neuronal integrity.
• Both AD and DM involve impaired glucose transport and mitochondrial dysfunction.
• ApoE4 genotype combined with dyslipidemia increases AD risk, common in DM.

Conclusions:

• Shared pathways, including insulin resistance, inflammation, and genetic factors, link AD and DM.
• Targeting shared mechanisms like insulin-degrading enzyme and HSP60 offers therapeutic potential.
• Developing treatments for the overlapping pathophysiology of AD and DM is crucial for effective management.