Alzheimer’s disease cause needs to be reconsidered, researcher says

Alzheimer’s disease research in the last two decades has focused on the theory that beta-amyloid plaque accumulates in the brain and leads to the loss of cognitive function. However, this theory has not produced advances in treating the disease, with many clinical trials on drugs targeted at amyloid plaques failing. A new hypothesis on the cause of Alzheimer’s should be considered, a leading researcher said Tuesday.

Age is the most important risk factor in the disease, said Karl Herrup, chairman of the department of cell biology and neuroscience at Rutgers University. Set against the backdrop of the natural, slow cognitive decline that everyone experiences with age, Herrup offers a new hypothesis to explain the disease.

He suggests three steps are involved in the development of Alzheimer’s disease. First, there is some type of vascular brain injury. This can be a type of physical head trauma that occurred earlier in life, small strokes that occur in old age or other types of vascular injury. Second, the brain responds to this injury with inflammation. However, the normal inflammatory response doesn’t shut itself off and becomes chronic and destructive. Finally, the cells of the brain are permanently altered and cannot return to a normal function.

In this model of the disease, beta-amyloid plaque can be part of the biology of Alzheimer’s disease but does not cause the disease.

“It allows that amyloid deposit is a risk factor. But, in my mind, it recalibrates the emphasis on amyloid and other aspects of the disease,” Herrup said.

The hypothesis points to other avenues of research, he said, such as using anti-inflammatory drugs early in the disease process or targeting therapies that would act on the physiological changes in brain cells that occur after long-term inflammation.

The theory also suggests that good cardiovascular health may prevent the disease cascade from beginning.

“Based both on my hypothesis and the reading of the field, anything you can do to retain your cardiovascular health is probably a good thing,” he said. “You are both helping to stave off the initiating injury and improving the vascular health of your brain.”

Herrup’s paper was published Tuesday in the Journal of Neuroscience. While the beta-amyloid hypothesis is still the predominant theory on the cause of the disease, Herrup said he believes that researchers in the field will consider other ideas.

“I see this as a work in progress,” he said. “It’s a very new way of looking at the disease. I think it’s an appropriate time to start looking at other hypotheses.”

Related: Another potential Alzheimer’s medication is a bust.

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