For First Time, Scientists “See” Both Alzheimer’s Markers in Drug Trial
Alzheimer’s disease is characterized by the presence of two signature markers in the brain – amyloid plaques and tau tangles. To date, most Alzheimer’s research into the causes of the disease and treatment/prevention strategies has focused on amyloid. Based on current research findings, however, tau build up in the brain correlates more closely with the memory and thinking decline of Alzheimer’s.
This week, the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) Study will begin scanning its clinical trial participants for the presence of tau – the first time researchers have collected images of both tau and amyloid simultaneously in an Alzheimer’s prevention trial. The A4 Study is testing whether a new investigational drug can slow the memory loss caused by Alzheimer’s disease in people ages 65-85 who have normal thinking and memory function but who may be at risk for developing Alzheimer’s memory loss in the future. In addition, through the amyloid and tau imaging scans, it may give us insights into how the two pathways affect the progression of memory loss and other symptoms caused by Alzheimer’s.
This research landmark comes about as a direct result of funding provided, in part, by the Alzheimer’s Association (see below).
Reisa Sperling, M.D., M.M.Sc., professor of neurology at Harvard Medical School, director of the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital and Massachusetts General Hospital, and co-principal investigator of the A4 Trial, told the Alzheimer’s Association that, “This will be the first tau PET scan done in an Alzheimer’s prevention trial. This is really exciting because it allows us to investigate whether decreasing amyloid can actually slow the progression of the tau tangles, which is so closely associated with cognitive impairment in Alzheimer’s.”
It is especially important to study this in the earliest stages of Alzheimer’s, where there are brain changes but before outward symptoms of memory or thinking problems. Research suggests that amyloid may “fan the flames” of tau – acting as an accelerant for tau spreading in the brain.
Alzheimer’s Association Involvement
In March 2014, the Alzheimer’s Association announced its largest ever research grant – $8 million over four years – to support the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) study as a companion study to the A4 Study, a pioneering Alzheimer’s prevention trial.
The A4 Study is a three-year, randomized, double-blind, secondary prevention trial of an anti-amyloid treatment. It will be conducted in 1,000 cognitively normal older individuals who show evidence of abnormal beta amyloid accumulation on PET imaging, which suggests that they are at risk for cognitive decline, but not yet experiencing symptoms.
The LEARN subcomponent of A4 will follow individuals who do not have elevated amyloid and determine what biological changes are related to cognitive decline, including increases in tau levels, helping to shed light on the individual variations in Alzheimer’s progression. They will be followed for 36 months, with identical clinical/cognitive testing performed every six months in parallel to the A4 Study.
The Association’s funding includes support for a companion study that utilizes cutting-edge tau PET imaging to make determinations about the role of tau in developing Alzheimer’s. The objectives of the tau PET imaging study are to qualify tau as a biological marker of developing Alzheimer’s and determine whether the build-up of tau in the brain is altered in response to anti-amyloid treatments.
All data generated through LEARN will be made publicly available and accessible to scientists though the Global Alzheimer’s Association Interactive Network (GAAIN™).
The $4 million lead gift that made this grant possible was from a private family foundation that is a member of the Alzheimer’s Association Zenith Society, which comprises the Association’s highest and most involved level of philanthropy.
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