Plasma beta amyloid and the risk of Alzheimer's disease in Down syndrome

Extracellular deposition of amyloid beta peptide (A beta) has been implicated as a critical step in the pathogenesis of Alzheimer's disease (AD). In Down syndrome (DS), Alzheimer's disease is assumed to be caused by the triplication and overexpression of the gene for amyloid precursor protein (APP), located on chromosome 21. Plasma concentrations of A beta 1-40 and A beta 1-42 were determined in a population based study of 506 persons with DS, who were screened annually for dementia. We used Cox proportional hazards models to determine the risk of dementia. Demented persons with DS have a significantly higher plasma A beta 1-40 concentration than the nondemented (p = 0.05). Those with the highest concentrations of A beta 1-40 and A beta 1-42 have a higher risk to develop dementia. The risk to develop dementia during follow-up (mean 4.7 years) increased to 2.56 (95% confidence interval, 1.39-4.71) for A beta 1-42 and 2.16 (95% confidence interval, 1.14-4.10) for A beta 1-40. High plasma concentration of plasma A beta 1-40 and A beta 1-42 are determinants of the risk of dementia in persons with DS. (C) 2012 Elsevier Inc. All rights reserved.