June 16, 2024
Alzheimer's Disease

Unraveling the Mystery: New Study Identifies Molecular Drivers of Alzheimer’s Disease at the Single-Cell Level

The Centers for Disease Control and Prevention (CDC) in the US reports that approximately 5.8 million Americans are currently grappling with Alzheimer’s disease, making it the most common form of dementia. Despite extensive research, there is still no cure for Alzheimer’s, largely due to a lack of understanding regarding its underlying causes. However, a groundbreaking study conducted by researchers at Scripps Research is shedding new light on the molecular drivers contributing to Alzheimer’s progression.

The researchers, led by clinical neurologist Stuart Lipton, MD, Ph.D., protein expert John Yates, III, Ph.D., and bioinformaticist Nicholas Schork, Ph.D., employed a novel technique to study single, living brain cells affected by Alzheimer’s disease. By measuring the electrical activity of individual neurons and examining protein levels within those cells, the scientists discovered new molecules linked to Alzheimer’s. These molecules could potentially be targeted by drugs to treat or slow the progression of the neurodegenerative disease in the future.

The collaborative efforts among the Scripps Research professors played a crucial role in the development of this breakthrough. Lipton, who is also the Step Family Foundation Endowed Professor and co-director of the Neurodegeneration New Medicines Center at Scripps Research, expressed his awe at the ability to measure one cell’s electrical activity at the order of one-millionth of one-millionth of an ampere and then examine thousands of proteins within the same cell. He further emphasized that this method allows for the discovery of novel targets for Alzheimer’s disease and related dementias.

Previous research by Lipton and his team has shown that certain neurons become overactive in the brains of individuals with Alzheimer’s, resulting in stronger or more frequent electrical signals. This overactivity, also known as hyperexcitability, is believed to contribute to the cognitive decline associated with Alzheimer’s.

In this new study, Lipton and his colleagues developed a system that enables precise measurements of individual brain cells and compares those affected by Alzheimer’s with healthy cells. Lipton’s group, which has previously pioneered methods for measuring the electrical activity of neurons, joined forces with Yates to use mass spectrometry to identify levels of over 2,250 proteins in each nerve cell. While mass spectrometry has traditionally been used to identify and quantify proteins from bulk collections of cells, recent advancements now permit measurements at the single-cell level.

1. Source: Coherent Market Insights, Public sources, Desk research.
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