High Brain Amyloid Levels Linked with Early Stage Alzheimer’s Disease

The first published findings from an ongoing Alzheimer’s prevention study by the National Institute of Aging support the hypothesis that higher levels of amyloid in the brain represent an early stage Alzheimer’s disease. The A4 trial, Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease, used PET scans to identify cognitively normal adults with high levels of amyloid accumulation in the brain to test whether the drug solanezumab could slow cognitive decline. The study is expected to end in late 2022.

The large number of people screened for A4 (4,486) gave investigators an unprecedented opportunity to assess differences in those with and without early evidence of amyloid build up in the brain. Those with higher amyloid levels, about one-third (1,323) of the total screened, were more likely to be older; have a family history of dementia; carry the APOE4 gene, which increases the risk of getting Alzheimer’s and at a younger age; and have lower cognitive test scores and report subtle changes in their own cognitive function. Elevated amyloid levels were not associated with differences in sex, education, marital or retirement status, or multiple self-reported lifestyle variables, such as exercise levels, smoking, caffeine or alcohol intake. 

“The A4 trial shows that we can identify people with Alzheimer’s disease early, when they have mild symptoms or even none at all, and that PET amyloid scan results appear to be a solid biomarker for the disease,” said Howard Fillit, MD, Founding Executive Director and Chief Science Office at the Alzheimer’s Drug Discovery Foundation. “This has important implications because it shows we can use biomarkers to ensure we’re enrolling the right people in Alzheimer’s prevention trials—that is, people very likely to have the disease.”

Before PET amyloid scans were available, researchers could not be certain they were testing amyloid targeting drugs in people who actually had high levels of the protein. The ADDF Diagnostics Accelerator is focused on the next important step—finding less expensive and more accessible biomarker tests for amyloid and other markers of Alzheimer’s disease. “Once we have a blood test available, these kinds of prevention trials will be even more efficient and less costly,” said Dr. Fillit. “Blood tests are easy to repeat—so they will be useful not only as a screening tool, but also as a way to measure drug effect over the course of clinical trials, which can take years.”

The National Institutes of Health have made the study data freely available to others in the Alzheimer’s research community. Researchers say this large pool of data will help improve the efficiency of screening and enrollment in newer trials designed to prevent Alzheimer’s in high-risk individuals who do not yet have symptoms of the disease.