# Bridging pathologies: Mechanistic insights into the diabetes–Alzheimer's nexus

## TL;DR

This paper reviews how diabetes and Alzheimer's disease share biological mechanisms and explores potential treatments that target both conditions.

## Contribution

The paper provides a comprehensive review of shared mechanisms between T2DM and AD, emphasizing the role of insulin signaling and metabolic therapies.

## Key findings

- Impaired insulin signaling and chronic inflammation are key overlapping mechanisms between T2DM and AD.
- Emerging antidiabetic treatments may modulate AD progression through gut-brain axis targeting.
- Biomarker development is critical for early detection and intervention in T2DM-AD comorbidity.

## Abstract

Type 2 diabetes mellitus (T2DM) is increasingly recognized as a major risk factor for Alzheimer's disease (AD), with mounting evidence highlighting shared pathophysiological mechanisms. This review explores the intricate biological and molecular links between these two chronic disorders. Key overlapping pathways include impaired insulin signaling, chronic inflammation, oxidative stress, mitochondrial dysfunction, amyloid-beta (Aβ) accumulation, tau hyperphosphorylation, and the formation of advanced glycation end-products (AGEs). Disruption of insulin signaling in the brain contributes to synaptic loss and neurodegeneration, while systemic metabolic disturbances aggravate blood-brain barrier dysfunction and neurovascular damage. Emerging studies also underscore the role of antidiabetic treatments, especially newer agents targeting the gut-brain axis, in modulating AD progression. The review further examines preclinical models, clinical observations, and the development of biomarkers to improve early detection and intervention. Despite growing insights, challenges remain in translating mechanistic knowledge into effective therapies. A multidisciplinary approach integrating metabolic control and neuroprotective strategies is essential for addressing the comorbid burden of T2DM and AD.

See also the graphical abstract(Fig. 1).