The most common form of dementia in the elderly is Alzheimer’s disease. This is usually characterized by plaques and tangles in the brain. Cure efforts are put towards finding these abnormal structures. Although, a research team has identified alternate chemistry that could account for the various pathologies associated with the disease.
Are Plaques and Tangles the Cause of Alzheimer’s
The main attention in curing Alzheimer’s disease has gone to plaques and tangles.
What are plaques and tangles?
- Plaques are deposits of a protein fragment called beta-amyloid.
- Tangles are twisted fibers of tau that look like bundles of fibers built up in cells.
The dominant theory based on beta-amyloid buildup has been around for decades, and dozens of clinical trials based on that theory have been attempted, but all have failed. Neurons are susceptible to lysosomal problems, which we report is a likely cause of Alzheimer’s disease.
What Happens In the Brain
An organelle within the cell, the lysosome serves as the cell’s trash can. Old proteins and lipids get sent to the lysosome to be broken down into their building blocks, which are then shipped back out to the cell to be built into new proteins and lipids.
The lysosome has a weakness when it does not get broken down into little pieces, then those pieces can’t leave the lysosome. The cell decides the lysosome is not working and stores it. If the new lysosome also fails, the process is repeated, resulting in lysosome storage.
The brains of people who have lysosomal storage disorder and the brains of people who have Alzheimer’s disease are similar in terms of lysosomal storage.
What Research Found
Long-lived proteins, including beta-amyloid and tau, can undergo spontaneous modifications that can make them undigestible by the lysosomes. Long-lived proteins become more problematic as we age and could account for the lysosomal storage seen in Alzheimer’s.
Enzymes that ordinarily break down the protein are unable to do so because they can’t latch onto the protein. It’s like trying to fit a left-handed glove on your right hand. These proteins undergo this chemistry that is almost invisible, which may explain why researchers have not paid attention to it.
What Modifications Take Place
It’s been long known that these modifications happen in long-lived proteins, but no one has ever looked at whether these modifications could prevent the lysosomes from being able to break down the proteins. One way to prevent this would be to recycle the proteins so that they are not sitting around long enough to go through these chemical modifications.
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