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2023 Alzheimer's Association Research Fellowship (AARF)

Hypothalamic Nuclei and the Spatiotemporal Evolution of Alzheimer’s disease

How does nerve cell loss in a region deep within the brain lead to early-stage Alzheimer’s?

Marion Baillet, Ph.D.
University of Liege
Liege, Belgium



Background

In Alzheimer’s , one of the earliest brain changes is a loss of nerve cells in a region called the hypothalamus. The hypothalamus regulates several important body functions – hormone secretion, sleep and appetite – that can impact memory and other cognitive functions. Recent studies have found that a particular area of the hypothalamus (the posterior hypothalamus) undergoes an especially large loss of nerve cells in early Alzheimer’s. It is not yet understand exactly how changes in the posterior hypothalamus lead to other brain changes in individuals with Alzheimer’s. 

In initial studies, Dr. Marion Baillet and colleagues examined brain samples from individuals who had Alzheimer’s or mild cognitive impairment (MCI, a condition of subtle memory loss that may precede Alzheimer’s). They found that samples with brain cell loss in the posterior hypothalamus had faster build-up of tau (a hallmark brain change in Alzheimer’s) in other parts of the brain. They also found that brain cell loss in the posterior hypothalamus continued throughout the progress of Alzheimer’s.

Research Plan

Dr. Baillet and colleagues will  examine about 1,000 brain samples from two large studies of aging. These samples will be from individuals who had Alzheimer’s, MCI or no cognitive impairment. Using sophisticated analytical techniques, the researchers will assess how the loss of nerve cells in the posterior hypothalamus impact brain accumulation of tau and beta-amyloid (another hallmark brain change in Alzheimer’s ), loss of nerve cells in other brain regions, as well as memory loss and other forms of cognitive decline over the course of Alzheimer’s. They will also assess how early hypothalamic brain cell loss begins in disease progression.

Impact

The results of this study could shed new light on the role of the hypothalamus in Alzheimer’s. They could also lead to novel methods of diagnosing and treating the disease at its earliest stages.

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