Scientific research has linked Alzheimer’s disease to a buildup of beta-amyloid plaques in the brain, which gum up mental functions and lead to memory loss and eventually death.

But a significant proportion of patients diagnosed with Alzheimer's don’t have any evidence of plaque buildup on PET scans or in autopsies, researchers have found, MedPage Today reports.

Researchers with Banner Alzheimer's Institute in Phoenix reported online in JAMA Neurology that an analysis of 200 patients clinically diagnosed with mild-to-moderate Alzheimer's disease showed that only 25 percent had beta-amyloid plaques in their brains.

This suggests other factors may be at work for some patients, and raises questions about plaque-based diagnostic methods and treatments.

"These patients are unlikely to respond to anti-amyloid treatment; they're unlikely to benefit from prevention with anti-amyloid drugs," said lead researcher Eric Reiman, M.D. "But this provides more support for the idea that in symptomatic patients with Alzheimer's and mild cognitive impairment, if you're going to study anti-amyloid therapy, make sure there's evidence of amyloid on PET or cerebrospinal fluid."

The findings are based on a review of data from the National Alzheimer's Coordinating Center on 200 mild-to-moderate Alzheimer's patients. Half of those individuals had mutations in the so-called APOE4 gene, associated with increased risk of Alzheimer's.

Overall, 50 of these patients —25 percent of the population studied — had no or very sparse amyloid plaques on post-mortem examination.

Dr. Reiman noted that the patients with Alzheimer's who have no evidence of plaques make up "a small but important percentage" of and that researchers "have a lot to learn about what's contributing" to these cases.

The study was supported by grants from the National Institute on Aging, the Arizona Alzheimer's Consortium, and the National Alzheimer's Coordinating Center.