Alzheimer's disease (AD) is a complex disease that can have a profound impact on individuals, families, and communities. There is currently no cure for Alzheimer's, but research has shown promise in targeting the underlying pathology of the disease, namely the accumulation of amyloid beta and tau proteins in the brain.
The Alzheimer's disease continuum begins with a long asymptomatic or preclinical stage, during which amyloid beta (Aβ) is accumulating for more than a decade prior to widespread cortical tauopathy, neurodegeneration, and the manifestation of clinical symptoms. This early stage of Alzheimer's disease is of particular interest to researchers, as it presents a potential window of opportunity for intervention and prevention of cognitive decline.
The AHEAD 3-45 Study is a research project investigating whether a drug called lecanemab can slow down the progression of Alzheimer's disease during its preclinical stage. Lecanemab is a humanized immunoglobulin 1 (IgG1) monoclonal antibody that preferentially targets soluble aggregated Aβ. By binding to Aβ and promoting its clearance, lecanemab has the potential to reduce the burden of amyloid pathology in the brain and prevent its downstream effects on tauopathy and neurodegeneration.
The study consists of two sister trials (A3 and A45) in cognitively unimpaired individuals aged 55 to 80 with specific dosing regimens tailored to baseline brain amyloid levels on screening positron emission tomography (PET) scans: intermediate amyloid (≈20 to 40 Centiloids) for A3 and elevated amyloid (>40 Centiloids) for A45. Both trials are being conducted under a single protocol, with a shared screening process and a common schedule of assessments.
The study's primary aim is to test whether lecanemab can slow the accumulation of tau and prevent the cognitive decline associated with AD during its preclinical stage. Eligibility to randomize into the A3 Trial or A45 Trial is based on the screening PET imaging results. This innovative design allows for the efficient identification of suitable participants and reduces the number of PET scans required, which can be expensive and time-consuming.
The AHEAD 3-45 Study, the authors of which include seven ATRI-affiliated faculty, is conducted as a Public-Private Partnership of the Alzheimer's Clinical Trial Consortium (ACTC), funded by the National Institute on Aging, National Institutes of Health (NIH), and Eisai Inc. ATRI helped design and manage the study through its ACTC partnership.
Research like The AHEAD 3-45 Study is vital in our ongoing fight against Alzheimer's disease. By targeting the disease's underlying pathology, we may be able to prevent the cognitive decline associated with AD and ultimately find a cure. As we continue to make progress in our understanding of the disease, we remain committed to advancing research efforts to improve the lives of those affected by Alzheimer's disease.
