2022 Alzheimer's Association Research Grant (AARG)

Impact of White Adipose Tissue on Tau Pathology in Transgenic Mice

How may body fat  promote the development of dementia-related tau protein in the brain?

David Baglietto-Vargas, Ph.D.
University of Malaga
Málaga, Spain

Background

As obesity prevalence increases worldwide, there are also increases in the consequences for overall health related to obesity. Obesity is associated with increased risk of type 2 diabetes, high blood pressure and other health factors that make up a condition called metabolic syndrome. This syndrome affects multiple systems in the body, including the brain, and it may raise the risk for dementia in older adults. Recently, scientists have been studying the role of white adipose tissue (a specific type of body fat) in dementia risk. In initial studies, Dr. David Baglietto-Vargas and colleagues injected white adipose tissue from obese mice into genetically-engineered Alzheimer’s-like mice. They found that this type of fat tissue promoted the development of abnormal tau protein — a variety of tau that is a hallmark brain change in Alzheimer’s which has been shown to promote brain cell damage and cell death.

Research Plan

Dr. Baglietto-Vargas and team will work to further understand the connection between white adipose tissue and dementia risk. To do this, they will inject mouse fat tissue into Alzheimer’s-like mice and determine how this increase in fat tissue impacts the biological underpinnings that lead to increases in the presence of disease-related tau. They will also assess how injected fat may change the activity of microglia, the resident immune cells of the brain. This could help determine the role of white adipose tissue in promoting abnormal tau, in part, related to changes in the brain’s immune system. Finally, the investigators will repeat a similar set of experiments using human white adipose tissue to inject into the mice to study abnormal tau and levels of inflammation. 

Impact

Results from Dr. Baglietto-Vargas’ project could shed new light on the links between obesity and tau in Alzheimer’s disease. This could also lead to novel therapies – including lifestyle-related interventions – for preventing or treating dementia.