The Brain-Heart Axis: Alzheimer's, Diabetes, and Hypertension

Abstract

Alzheimer's disease (AD) is a debilitating neurodegenerative disorder affecting millions worldwide. Currently, there are only four approved treatments for AD, which improve symptoms modestly. AD is believed to be caused by the formation of intercellular plaques and intracellular tangles in the brain, but thus far all new drugs which target these pathologies have failed clinical trials. New research highlights the link between AD and Type II Diabetes (T2D), and some believe that AD is actually a brain specific form of it termed Type III Diabetes (T3D). Drugs which are currently approved for the treatment of T2D, such as metformin, have shown promising results in improving cognitive function and even preventing the development of AD in diabetic patients. Recent studies shed light on the relationship between the brain and cardiovascular system in which the brain and heart communicate with one another via the vasculature to regulate fluid and nutrient homeostasis. This line of research reveals how the brain-heart axis regulates hypertension and diabetes, both of which can impact cognitive function. In this review we survey past and ongoing research and clinical trials for AD, and argue that AD is a complex and systemic disorder which requires comprehensive approaches beyond the brain for effective prevention and/or treatment.

Figure 1

Depiction of renin angiotensin (RAS) and natriuretic peptide (NP) players and their expression levels in the brain. Blue text refers to the controversial nature of whether renin is expressed in the brain: (∗) only protein detected, not mRNA; (+) expressed; (±) expressed at lower levels compared to other cell types.

Figure 2

Diagram depicting the interconnection of diabetes, hypertension, cardiovascular disease, and AD and how disease progression has been targeted clinically thus far. Causative factors driving increased circulating Aβ and IGF resistance in the brain (blue text) remain incompletely understood despite being tightly linked to AD pathogenesis.