Elevated Plasma β-Amyloid Peptide Aβ42 Levels, Incident Dementia, and Mortality in Down Syndrome

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Abstract
Alzheimer disease (AD) is associated with deposition of extracellular β amyloid in neuritic plaques and vessel walls, as well as intracellular accumulation of neurofibrillary tangles. β-Amyloid peptides Aβ40 and Aβ42, the 2 major species of β amyloid, are generated from the amyloid precursor protein by sequential proteolytic cleavage by β and δ secretases.1 Previous studies have demonstrated that brain levels of Aβ42 increase early in the development of dementia and decrease with cognitive decline.2 In cerebrospinal fluid, Aβ42 levels are reduced in patients with AD. In the elderly with mild cognitive impairment, low cerebrospinal fluid Aβ42 and high tau concentrations predict incipient AD.3 However, the relation of plasma concentration of Aβ42 and Aβ40 is less consistent. Although elevated plasma Aβ42 levels in nondemented participants have been associated with increased risk for AD, mild cognitive impairment, and cognitive decline,2,4-7 a recent large prospective study found that high levels of Aβ40 in conjunction with low levels of Aβ42 predicted the development of dementia.8