Alzheimer’s Update

Each year, the NARFE-Alzheimer’s National Committee determines which research projects will be awarded grants from the NARFE-Alzheimer’s Research Fund.

NARFE has awarded a total of 85 research grants since the program began in 1985. In 2021, NARFE members donated $278,127 to the fund. Therefore, at its virtual September meeting, the committee awarded two new grants totaling $278,127. This year’s grants were awarded to:

Ph.D., Indiana University, (Bloomington, IN), $175,000; fully funded over three years for his research on “The Role of Bassoon in Tau Pathophysiology and Propagation.”

This study will look at the way a brain cell’s nutrient and energy transport system is organized in parallel strands like railroad tracks and how these tracts allow nutrients to travel across the cell, delivering key materials that keep it healthy. The tau protein helps keep these tracks straight. However, in the brains of those with Alzheimer’s, frontotemporal dementia and more than 20 other brain diseases known collectively as “tauopathies,” the shape of tau protein becomes abnormally modified. This could contribute to the formation of tau “tangles,” which are characteristic brain changes of these diseases and of subsequent nerve cell damage.

In prior research, Dr. Martinez Contreras and his colleagues found that the abnormal tau may interact with other proteins, particularly one called bassoon, that could help transport it across different brain regions. By using genetically engineered Alzheimer’s-like mice, the researchers found that bassoon may be associated with the accumulation and transportation of abnormal tau in mouse brains. The researchers also found that when they reduced the activity of bassoon in the Alzheimer’s-like mice, the accumulation of tau in their brains decreased, potentially affecting nerve cell function.

Dr. Martinez Contreras and his colleagues will leverage their preliminary findings to further study how bassoon may be associated with the accumulation of abnormal tau and test whether genetic variations in the bassoon gene may increase accumulation and movement of abnormal tau in the brains of Alzheimer’s-like mice. The researchers will then compare their findings with that from Alzheimer’s-like mice that do not have genetic variations in the bassoon gene.

The results of this study may help researchers better understand the biological mechanisms by which abnormal tau accumulates and is transported in the brains of those who have Alzheimer’s disease and other tauopathies. The findings could reveal a potentially new therapeutic target for abnormal tau-related brain diseases, including Alzheimer’s.

Brigham and Women’s Hospital, (Boston, MA), $103,127 out of $174,497 (partial funding over three years) for her research on “The Ubiquitin-Proteasome System in the Degradation of Tau in Alzheimer’s Disease Neurons.”

This study will investigate how the clearance of nerve cell waste may be associated with brain changes observed in those with Alzheimer’s. The abnormal accumulation of the proteins beta-amyloid and tau to form “plaques” and “tangles,” respectively, are the two main hallmark brain changes observed in people who have Alzheimer’s. This may occur, in part, when the nerve cell’s structure, which acts like a garbage disposal and removes unwanted proteins, does not function properly.

In preliminary studies, Dr. Hsieh and her colleagues used data from the Religious Order Study and the Memory Aging Project (ROSMAP), an extensive study of aging and Alzheimer’s, to then look into a specialized type of stem cell, induced pluripotent stem cells (iPSCs), collected from adult human tissue. These iPSCs can be programmed to grow into any type of cell in the body, including brain nerve cells. Using these cells, the team studied brain changes in the initial stages of Alzheimer’s. They found that proteasomes may not function

properly in some nerve cells, even before the cells have tau tangles.

The researchers also used a specific measure to analyze small changes in genes to study a person’s risk of developing a disease. Dr. Hsieh’s team found that the levels of proteasomes in the nerve cells may be associated with this measure. Based on these findings, the researchers believe that proteasomes may become impaired in the early stages of Alzheimer’s, and this could be associated with brain changes, including levels of plaques and tangles in the brain, in later stages of the disease.

Using advanced microscopic and statistical techniques, Dr. Hsieh and her colleagues will investigate proteasome function in nerve cells from iPSCs from various individuals with Alzheimer’s and from cognitively unimpaired individuals in the ROSMAP project. They also aim to identify genetic factors that regulate the proteasomes in the brain and study the potential association between the activity of proteasomes and the levels of tangles over time.

Results from this study may provide a better understanding of how the clearance of cellular waste may be associated with brain changes observed in people with Alzheimer’s, and the findings may point to potential therapeutic strategies that could improve proteasome activity.

OLIVIA A. WILLIAMS IS CHAIR OF THE NARFE-ALZHEIMER’S NATIONAL COMMITTEE. EMAIL: OEASHF3@GMAIL.COM. THIS COLUMN APPEARS QUARTERLY.

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