Abstract
Extracellular deposition of amyloid beta peptide (Abeta) 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 Abeta1-40 and Abeta1-42 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 Abeta1-40 concentration than the nondemented (p = 0.05). Those with the highest concentrations of Abeta1-40 and Abeta1-42 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 Abeta1-42 and 2.16 (95% confidence interval, 1.14-4.10) for Abeta1-40. High plasma concentration of plasma Abeta1-40 and Abeta1-42 are determinants of the risk of dementia in persons with DS.
