2024 Alzheimer's Association Research Fellowship (AARF)

S14 Sphingomyelin – The Link Between Obesity and Alzheimer’s Disease

What are the biological mechanisms linking western diet-induced obesity and cognitive impairment? 

Roisin McManus, Ph.D.
German Center for Neurodegenerative Diseases
Bonn, Germany

Background

As obesity prevalence rises worldwide, there are also increases in the consequences for overall health. Obesity is associated with an increased risk of type 2 diabetes, metabolic disorders, and vascular (blood vessel) disorders, which impact multiple systems in the body, including the brain, and may increase one’s risk of developing Alzheimer’s. 

One contributor to increased obesity rates is the adoption of a western diet (characterized by a high intake of ultra-processed foods, fat, sugar, salt, alcohol, and refined grains, and a reduced consumption of fiber, fruits, and vegetables). Previous studies in humans and mice show that western diet-induced obesity and vascular disease are associated with an increase in a specific type of lipid (fat) in the blood called sphingomyelin 14 (S14). Other research indicates that the dysregulation of lipids such as S14 may play a role in chronic brain inflammation and the aggregation of beta-amyloid in the brain. Dr. Róisín McManus and colleagues believe that S14 may act as a link between risk factors such as obesity and the development of Alzheimer’s.

Research Plan

Dr. McManus and the team will study whether S14 is the biological signal linking obesity with cognitive decline and Alzheimer’s. The researchers believe obesity-induced S14 may activate the brain’s primary immune cells, called microglia, and sensitize them to the accumulation of beta-amyloid in the brain. They will study biological samples from genetically engineered Alzheimer’s-like mice, cognitively unimpaired mice, and individuals with and without cognitive impairment to determine how obesity-induced S14 may trigger microglial activity and impact microglial function. 

Impact

The results of this study may help improve our understanding of how obesity is linked to Alzheimer’s risk. These findings may also inform future strategies for preventing Alzheimer’s.