Alzheimer’s disease trial links high amyloid levels with early stage disease

Alzheimer's disease trial links high amyloid levels with early stage disease

Findings from a new trial have highlighted that higher levels of the amyloid protein in the brain represent an early stage of Alzheimer’s disease.

The data from the trial has been published from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) study. The findings support the hypothesis that higher levels of the protein represent an early stage of Alzheimer’s disease, and also show that amyloid burden in clinically normal older adults is associated with a family history of disease, lower cognitive test scores, and reports of declines in daily cognitive function.

The findings have been published in the journal JAMA Neurology.

Could we slow cognitive decline?

The A4 study is an ongoing prevention trial launched in 2014 to test whether the drug solanezumab, a monoclonal antibody, could slow cognitive decline associated with elevated brain amyloid if started before clinical symptoms appear.

Amyloid, long considered a hallmark of Alzheimer’s disease, has been the target of therapies in clinical trials in people who already show symptoms of the disease.

NIA Director, Richard Hodes, said: “A4 is pioneering in the field because it targets amyloid accumulation in older adults at risk for developing dementia before the onset of symptoms.

“A major issue for amyloid-targeting Alzheimer’s disease clinical trials, and one that is being addressed with the A4 study, is that previous trials may have been intervening too late in the disease process to be effective.”

Laurie Ryan, PhD, chief of the Dementias of Aging branch in NIA’s Division of Neuroscience, said: “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.

“Before the availability of amyloid PET, other amyloid-targeting clinical trials may have been testing therapies in some people who didn’t have amyloid.”

This new data will help improve efficiency of screening and enrolment of other trials designed to prevent Alzheimer’s in people without symptoms.

“A4 demonstrates that prevention trials can enrol high risk individuals, people with biomarkers for Alzheimer’s who are cognitively normal,” said Ryan, adding, “Ultimately, precision medicine approaches will be essential.”

“Alzheimer’s disease is never going to have a one-size-fits-all treatment,” she said. “We’re likely to need different treatments, even combinations of therapies, for different individuals based on their risk factors.”

NIA’s diverse Alzheimer’s disease and related dementias research portfolio includes about 230 clinical trials. Of these, more than 100 are focussed on non-pharmacological interventions, including but not limited to diet, exercise and cognitive training. Of the current 46 pharmacological trials supported by NIA, most investigate targets other than amyloid, such as neuroprotection and inflammation.

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