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Extracellular deposition of amyloid beta peptide (Aβ) 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 Aβ1-40 and Aβ1-42 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 Aβ1-40 concentration than the nondemented (p = 0.05). Those with the highest concentrations of Aβ1-40 and Aβ1-42 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 Aβ1-42 and 2.16 (95% confidence interval, 1.14-4.10) for Aβ1-40. High plasma concentration of plasma Aβ1-40 and Aβ1-42 are determinants of the risk of dementia in persons with DS.

Original publication

DOI

10.1016/j.neurobiolaging.2011.08.007

Type

Journal article

Journal

Neurobiology of aging

Publication Date

09/2012

Volume

33

Pages

1988 - 1994

Addresses

Dichterbij, Center for the Intellectually Disabled, Gennep, The Netherlands. a.coppus@erasmusmc.nl

Keywords

Humans, Alzheimer Disease, Down Syndrome, Peptide Fragments, Disability Evaluation, Proportional Hazards Models, Retrospective Studies, Follow-Up Studies, International Classification of Diseases, Aged, Aged, 80 and over, Middle Aged, Community Health Planning, Netherlands, Female, Male, Amyloid beta-Peptides