High Amyloid Levels Associated with Early Stage Alzheimer’s Disease

A study published in JAMA Neurology has supported earlier findings that Alzheimer’s disease is associated with higher levels of amyloid protein in the brain and has further discovered that early interventions with a drug (solanezumab) in clinically normal individuals slows cognitive decline.

The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) study, conducted by lead author Reisa A. Sperling, M.D., at Brigham and Women’s Hospital and Harvard Medical School, will finish in 2022. It is a prevention trial to study solanezumab, a monoclonal antibody that is currently under investigation for Alzheimer’s, and its efficacy in decreasing cognitive decline linked with increased amyloids in the brain if it starts before symptoms appear.

The building of amyloids (a type of protein) is the hallmark of Alzheimer’s disease. It clumps together to form sticky plaques in the spaces between nerve cells, causing nerve cells in the brain to die. Alzheimer’s, a subset of dementia, affects 50 million people worldwide, and according to calculations it will target 150 million people by 2050. Alzheimer’s disease is the most common form of dementia and may contribute to 60-70% of all cases of dementia.

Source: WHO

The team of researchers looked for normal cognitive people with high amyloid levels. 15,000 people were screened who were interested in the study. Out of 150,00, some 6,763 volunteers were brought in for testing, assessment and genotyping. 2,277 participants were excluded due to medical reasons whereas 4,486 participants were tested with positron emission tomography (PET). PET imaging revealed 1,323 people with elevated amyloid levels who were eligible to continue in the A4 study.

Dr. Laurie Ryan, chief of the Dementias of Aging Branch in NIA’s Division of Neuroscience, says:

In 2014, A4 was a first-of-its-kind study because it used amyloid PET to identify cognitively normal people with high levels of brain amyloid. A4 demonstrates that prevention trials can enroll in high-risk individuals. Ultimately, precision medicine approaches will be essential. Alzheimer’s disease is never going to have a one-size-fits-all treatment. We’re likely to need different treatments, even combination of therapies, for different individuals based on their risk factors.

NIA Director, Dr. Richard J. Hodes, believes that usually the screening of patients and interventions are made so late that they are no longer effective on them. A4 trial is different from others because it intervenes when the disease has not progressed.

NIA Alzheimer’s and related dementias portfolio includes 230 clinical trials, with over 100 of them focusing on non-medicinal interventions such as diet therapy, exercise and cognitive training whereas 46 are medicinal trails.

Screening data for 4,486 individuals has been made available for researchers. This will help other researchers in the screening of Alzheimer’s disease and to stop it in people without symptoms. The research was funded by NIH grants.

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