ABSTRACT
Extracellular deposition of amyloid beta peptide (Aß) 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 Aß1-40 and Aß1-42 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 Aß1-40 concentration than the nondemented (p = 0.05). Those with the highest concentrations of Aß1-40 and Aß1-42 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 Aß1-42 and 2.16 (95% confidence interval, 1.14-4.10) for Aß1-40. High plasma concentration of plasma Aß1-40 and Aß1-42 are determinants of the risk of dementia in persons with DS.
