Association of Low Plasma Aβ42/Aβ40 Ratios With Increased Imminent Risk for Mild Cognitive Impairment and Alzheimer Disease

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Abstract
There is a growing consensus that the best way to manage Alzheimer disease (AD) will ultimately be through preventive therapy similar to that used for atherosclerotic heart disease. To facilitate preventive therapy, it is important to develop AD-related biomarkers that can be used to identify at-risk individuals in the same way that cholesterol levels are used to identify those at risk for atherosclerotic heart disease. In 1998, the Consensus Report of the Working Group on Molecular and Biochemical Markers of Alzheimer Disease1 proposed that an ideal diagnostic marker for AD should be reliable, able to detect a fundamental feature of AD neuropathology, and validated through confirmed cases. In addition, it should be noninvasive, simple to perform, and inexpensive. These criteria apply equally well to premorbid and diagnostic biomarkers. In this study, we evaluated plasma amyloid β protein (Aβ40 and Aβ42) and the Aβ42/Aβ40 ratio as premorbid biomarkers for AD and the amnestic type of mild cognitive impairment (MCI),2 which usually precedes AD.