International research initiatives in Alzheimer’s disease

Abstract

With continuing population increases and increasing life expectancy, ~100 million individuals worldwide will be affected with Alzheimer disease in 2050. Dementia was the fifth largest cause of death globally in 2016 and its annual global costs are US $315 billion. The absence of truly effective AD therapies ensures that these costs will steadily increase for the foreseeable future. Targeting lifestyle factors such as physical activity, dietary guidance, and attention to metabolic and vascular health may prevent cognitive decline in older adults. There also has been the advent of “secondary prevention” trials of experimental anti-Alzheimer drugs in cognitively normal individuals with elevated risk for developing symptomatic AD because they carry a pathogenic mutation that causes AD or have positive molecular AD biomarker studies (i.e., amyloid PET; CSF assays of Aβ42 and tau). The goal of secondary prevention trials is to delay or even avert the occurrence of symptomatic AD. Although studies of autosomal dominant AD (ADAD) have greatly advanced understanding of AD pathophysiology, it is as yet uncertain whether ADAD is a clone of the far more common “sporadic” late onset AD (LOAD). Two international multi-center studies of molecular biomarkers to characterize preclinical and early symptomatic AD, DIAN (ADAD) and ADNI (LOAD), were examined as to whether biomarker profiles in these disorders were similar or different. Both groups had largely identical AD biomarker profiles, suggesting that they share a common pathophysiology. There thus is cautious optimism that secondary prevention trial results in ADAD will extrapolate to LOAD.