**Author details**

426 Understanding Alzheimer's Disease

T2DM

VASCULAR DYSFUNCTION

• Breakdown of BBB and NVU • Dysfunctional hemodynamics • Cerebral Amyloid Angiopathy • Dysfunctional Aβ clearance

> • Hypoxia • Hyperglycemia • Increased BACE1

CEREBRAL HYPOPERFUSION and INCREASED Aβ

CEREBRAL ENERGY DEPLETION

NEURODEGENERATION

injury/dysfunction • Defects in neurogenesis • Cognitive impairments

• Synaptic

AD

• Oxidative stress • Inflammatory response

• Amyloidogenic processing of APP • Decreased Aβ degradation

**Figure 4.** Vascular hypothesis of AD. The vascular complications have been casually linked to the progression of AD. Vascular dysfunction resulting from type 2 diabetes results in a state of cerebral hypoperfusion, leading to significant

While AD remains a disease of more questions than answers, a wide array of evidence suggests a close relationship between AD and T2DM. T2DM has been characterized as having both macrovascular and microvascular complications that result in CVD. It is the vasculature that provides the tangible pathological link between T2DM and AD. Significant data has been collected in favor of the vascular hypothesis of AD, which is founded on the idea that pre-

energy depletion in the brain. Neurodegeneration results in cognitive impairments and ultimately AD.

existing CVD sets into motion pathological cascades that ultimately result in AD.

Brent D. Aulston1,2, Gary L. Odero1 , Zaid Aboud1,2 and Gordon W. Glazner1,2

1 St. Boniface Hospital Research Centre, Winnipeg, MB, Canada

2 Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, Canada
