Timeline: Our Key Moments in Brain Health Research

Our program on brain health launches!

The overarching goals? To understand the factors that contribute to brain health and develop therapies for dementia, including Alzheimer's disease.
In our first study, we investigated the link between impaired metabolism in a mouse model of diabetes with Alzheimer's disease brain pathology.

We discovered that brain neurons, the cells that transmit signals and form memories, can become non-responsive to insulin, the molecule that stimulates sugar metabolism. 

Our clinical study of people with diabetes and neuropathy, nerve damage in the feet and hands, found they also have an imbalance in brain levels of neurotransmitters, the molecules that transmit brain signals. 

We furthered our preclinical studies in diabetes mouse models, demonstrating that they develop Alzheimer's disease pathology in the brain through changes in a protein called tau. 

We showed that the brain of a diabetes mouse model develops insulin resistance, an insensitivity to insulin and sugar metabolism, which is linked to tissue pathology in Alzheimer's disease and the protein tau. 

A busy year for us!

• One study found that oxidized cholesterol, which is elevated in diabetes, impairs the function of brain lysosomes, cellular structures that clear debris. If debris is not cleared, this increases the risk of dementia; thus, this work highlighted another link between dysfunctional metabolism (diabetes) with poor brain health.
• Another study this year found that obesity in mice induces a process called endoplasmic reticulum stress in the brain, a cellular response to stress linked to dementia. 
• This year, we also launched our program on stem cells for treating dementia and Alzheimer's disease. Stem cells support and nurture brain neurons. These stem cells also produce a hormone called insulin-like growth factor-I, which stimulates metabolism and growth. 

We successfully demonstrated that we can transplant stem cells producing the hormone insulin-like growth factor I into the brain of Alzheimer's disease mice. 

We continued to develop and advance our stem cell program, discovering that insulin-like growth factor I expressing stem cells transplanted into the brain enhance memory in Alzheimer's disease mice. 

We demonstrated that obesity also impacts the pathology of another Alzheimer's disease protein called amyloid precursor protein. Further, we found that insulin-like growth factor I prevents this pathology.

We reported that cognitive performance is impaired in a severely obese population relative to lean control and that waist circumference (abdominal obesity) is a key metabolic risk factor for cognitive decline.

• Our 2021 Mini Symposium series focused on brain health topics.
• The Andrea and Lawrence A. Wolfe Brain Health Initiative is launched to support important research related to brain health and healthy brain aging.
• Our findings demonstrated that a diet rich in saturated fats (red meat) cause increased body weight and poor nerve function, while a diet rich in unsaturated fats (olive oil and avocado) had no effect on nerve function. We connected this to mitochondria, the machinery that generates energy in nerves.
• New funding from the NIH enabled us to launch the CLARiFY Diabetes Complications study in partnership with Australian colleagues. This clinical study which followed persons with type 1 diabetes since the 1990s, will enhance our understanding of how diabetes control over 30 years impacts brain structure and function.

• We used MRI (magnetic resonance imaging) to track the movement of transplanted stem cells in the brain of animal models. The MRI showed that the stem cells survive in the brain for as long as ten weeks. 

New initiatives this year include an NIH-funded project examining the effects of diet and exercise on nerve function and brain health in mouse models of obesity, prediabetes, and diabetes, as well as studies harnessing the power of stem cells to understand how different nerve and supporting glial cells impact brain health and metabolism.