In a new study, researchers found have identified a new target in the development of Alzheimer’s disease (AD) that could lead to therapies focused on treating the disease early in its progression.
They discovered a pathway that is accessible to detection and potential treatment, prior to much of the disease’s damage and well before clinical symptoms appear
The discovery could help bolster a promising approach to AD research: finding and manipulating processes earlier in the disease’s development with hopes of slowing its advance.
The research was conducted by a team at Case Western Reserve University.
First identified more than 100 years ago, AD is an age-related neurodegenerative disorder that is linked to deposits of plaques of amyloid-beta protein and tangles of tau protein in the brain, along with progressive nerve cell death.
Most AD diagnoses are in patients 65 or older, so identifying the disease in younger patients can be difficult.
Many patients experience a big loss in their brain’s white matter—central to cognition, emotion and consciousness—before receiving a diagnosis.
The cause of AD is not known, and the greatest risk factors for developing AD are age, genetics, and a previous traumatic brain injury.
Before the defining pathological characteristics of the disease are in place, the new pathway researchers can be targeted by potential therapeutics that aim to mitigate the degeneration of white matter that impairs the normal functions of brain circuitry.
Researchers found that the pathway plays a key role in disrupting the normal function of brain cells that produce the protective white matter sheathing for nerves, known as myelin.
The dysfunction and eventual death of these myelin-producing cells are well-established early events in AD that lead to cognitive deficits.
The new findings illuminate how these cells start to go awry: the over-expression of a certain protein (Drp1) within the recently discovered pathway.
It’s the hyperactivation of Drp1 protein that triggers inflammation and injury, culminating in a reduction of myelin—slowing communication in the brain—which leads to the degeneration of white matter and significant cognitive impairment.
The researchers hoped to target and manipulate the pathway with therapies that regulate the expression of Drp1, thereby slowing or reducing damage to myelin-producing cells.
They found that eliminating Drp1 expression could correct the energy-related defect in the cells.
This approach also reduced the activation of inflammation in the cells, lessened tissue damage at those brain sites and improved cognitive performance.
This could help reduce the downstream cascade of abnormal brain functions linked to the progression of AD.
The team says if therapies targeting this pathway can slow, stop, or even reverse early-stage AD progression, then possibly there can be a reduction or delay to later stage damage and impairments.
They validated the discovery of the pathway using mouse models and post-mortem brain samples of AD patients.
One author of the study is Xin Qi, a professor in the Department of Physiology and Biophysics.
The study is published in Science Advances.
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