In a new study, researchers have discovered alternate chemistry that could account for the various pathologies associated with Alzheimer’s disease.
The research was conducted by a team from the University of California, Riverside.
Alzheimer’s disease is the most common cause of dementia among the elderly.
Plaques and tangles have so far been the focus of attention in this progressive disease that currently afflicts more than 5.5 million people in the United States.
Plaques, deposits of a protein fragment called beta-amyloid, look like clumps in the spaces between neurons.
Tangles, twisted fibers of tau, another protein, look like bundles of fibers that build up inside 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
In the study, the team found in addition to plaques, lysosomal storage is observed in the brains of people who have Alzheimer’s disease.
Neurons—fragile cells that do not undergo cell division—are susceptible to lysosomal problems, specifically, lysosomal storage, which is a likely cause of Alzheimer’s disease.
According to the researchers, an organelle within the cell, the lysosome serves as the cell’s trashcan.
Old proteins and lipids get sent to the lysosome to be broken down to their building blocks, which are then shipped back out to the cell to be built into new proteins and lipids.
To maintain functionality, the synthesis of proteins is balanced by the degradation of proteins.
The lysosome, however, has a weakness: If what enters does not get broken down into little pieces, then those pieces also can’t leave the lysosome.
The cell decides the lysosome is not working and “stores” it, meaning the cell pushes the lysosome to the side and proceeds to make a new one.
If the new lysosome also fails, the process is repeated, resulting in lysosome storage.
The team says the brains of people who have lysosomal storage disorder, another well-studied disease, and the brains of people who have Alzheimer’s disease are similar in terms of lysosomal storage.
But lysosomal storage disorder symptoms show up within a few weeks after birth and are often fatal within a couple of years.
Alzheimer’s disease occurs much later in life. The time frames are, therefore, very different.
The researchers suggest long-lived proteins 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, an age-related disease.
If the findings are confirmed, it would open up new avenues for treatment and prevention of this disease.
The findings could also have implications for other age-related diseases such as macular degeneration and cardiac diseases linked to lysosomal pathology.
Next, the team will examine the extent of the protein modifications in human brains as a function of age.
The researchers will study brains of people with Alzheimer’s disease as well as of people not afflicted by it.
The lead author of the study is Ryan R. Julian, a professor of chemistry.
The study is published in ACS Central Science.
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