RUTGERS (US) — Age-related changes, like plaques and tangles, only lead to a slow natural decline in cognitive function; they don’t in themselves cause Alzheimer’s disease, according to a new hypothesis.
Alzheimer’s disease is an incurable, degenerative and eventually fatal disease that attacks cognitive function. It affects more than 26 million people around the world and is the most common form of dementia among people over the age of 65.
Three key steps are needed for an individual to progress from this natural path to the full spectrum of Alzheimer’s clinical symptoms: An initiating injury that is probably vascular in nature; an inflammatory response that is both chronic and unique to Alzheimer’s; and a cellular change of state, a one-way cell biological door that permanently alters the physiology of neurons and several other cell types in the Alzheimer’s disease brain.
“The initiating injury might trigger a protective response in the brain cells,” says Karl Herrup, professor of cell biology and neuroscience at Rutgers.
“But the real problem is that in the elderly the response doesn’t know when to quit. It continues even after the injury itself subsides. In the end, the real damage is done by the persistence of the response and not by the injury itself.”
Herrup’s research is reported in the Journal of Neuroscience.
Over the last three decades, most Alzheimer’s research has focused on the “amyloid cascade hypothesis,” that holds that the beta-amyloid peptide is the key to the initiation and progression of Alzheimer’s.
The theory has been popular because the peptide is the main ingredient of the disease-related plaques that are common in the brains of those affected.
The new theory should stimulate discussion and open the way to new experimental and diagnostic advances, Herrup says. “This new hypothesis, for example, emphasizes the value of anti-inflammatory approaches to the prevention of Alzheimer’s disease.”
While the individual components of the model aren’t entirely new, rearranging their order and shifting their priority has enormous implications for modern Alzheimer’s research.
“My hypothesis implies that beta-amyloid aggregation is not a central part of the biology of Alzheimer’s disease,” Herrup says. “It predicts that one can have plaques without having Alzheimer’s and that one can have Alzheimer’s without having plaques.
“Researchers should be cautious about following up these predictions, but since we’ve gone about as far as we can with our current hypothesis, we may have reached a point where too much caution is ill-advised.
“It’s time to re-imagine Alzheimer’s disease, so we can think creatively about treating it.”
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