The Relationship of Plasma Aβ Levels to Dementia in Aging Individuals With Down Syndrome

Department of Neurology, Georgetown University Medical Center, Washington, DC, USA.
Alzheimer disease and associated disorders (Impact Factor: 2.44). 07/2009; 23(4):315-8. DOI: 10.1097/WAD.0b013e3181aba61e
Source: PubMed

ABSTRACT To study the relationship between plasma levels of amyloid beta (Abeta) peptides and dementia in aging individuals with Down syndrome, we investigated the relationship among plasma Abeta, apolipoprotein E genotype and cognitive and clinical factors using baseline specimens form participants in an ongoing clinical trial in individuals with Down syndrome 50 years of age and older. Because of substantial skew in the distribution of peptide levels, analyses used log transformations of the data. The ratio of Abeta42 to Abeta40 was associated with the presence of dementia (P=0.003, df=196, F=9.37); this association persisted after adjustment for age, sex level of mental retardation, and apolipoprotein E genotype. Consistent with recent reports regarding the effect of presenilin mutations on peptide generation, our finding supports the theory that the ratio of Abeta42 to Abeta40 rather than absolute levels of the peptides is important to the pathophysiology of Alzheimer's disease in genetically susceptible populations.

6 Reads
  • Source
    • "Missense mutations in the gene for APP, which increase the proteolytic conversion of APP into the fibrillogenic Ab42 peptide, have been shown to lead to early onset of AD (Goate et al., 1991; Guerreiro et al., 2012; Rogaeva et al., 2007; Scheuner et al., 1996; Younkin, 1997), but less work has been done on the relation of common SNPs in APP to age at onset, risk of AD, or individual differences in Ab peptide levels (Benitez et al., 2013; Chapman et al., 2013; Kimura et al., 2007; Shulman et al., 2013). Several, but not all, studies have found a relationship between high initial levels of Ab42 and subsequent development of AD, both among adults with Down syndrome (Coppus et al., 2012; Head et al., 2011; Jones et al., 2009; Matsuoka et al., 2009; Schupf et al., 2001, 2007) and in the general population (Blasko et al., 2010; Mayeux et al., 1999, 2003; Pomara et al., 2005; Schupf et al., 2008). However, large GWAS studies of AD have not found an association between SNPs in APP and late onset AD (LOAD) (Bertram and Tanzi, 2012; Hollingworth et al., 2011; Lambert "
    [Show abstract] [Hide abstract]
    ABSTRACT: We examined the contribution of candidates genes for Alzheimer's disease (AD) to individual differences in levels of beta amyloid peptides in adults with Down syndrom, a population at high risk for AD. Participants were 254 non-demented adults with Down syndrome, 30-78 years of age. Genomic deoxyribonucleic acid was genotyped using an Illumina GoldenGate custom array. We used linear regression to examine differences in levels of Aβ peptides associated with the number of risk alleles, adjusting for age, sex, level of intellectual disability, race and/or ethnicity, and the presence of the APOE ε4 allele. For Aβ42 levels, the strongest gene-wise association was found for a single nucleotide polymorphism (SNP) on CAHLM1; for Aβ40 levels, the strongest gene-wise associations were found for SNPs in IDE and SOD1, while the strongest gene-wise associations with levels of the Aβ42/Aβ40 ratio were found for SNPs in SORCS1. Broadly classified, variants in these genes may influence amyloid precursor protein processing (CALHM1, IDE), vesicular trafficking (SORCS1), and response to oxidative stress (SOD1). Copyright © 2015 Elsevier Inc. All rights reserved.
    Neurobiology of aging 06/2015; 36(10). DOI:10.1016/j.neurobiolaging.2015.06.020 · 5.01 Impact Factor
  • Source
    • "ELISA 6E10 R182 R165 - - - - =  - Matsuoka et al. 2009 [53] "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cerebrospinal fluid and positron emission tomography biomarkers accurately predict an underlying Alzheimer's disease (AD) pathology; however, they represent either invasive or expensive diagnostic tools. Therefore, a blood-based biomarker like plasma amyloid beta (Aβ) that could correlate with the underlying AD pathology and serve as a prognostic biomarker or an AD screening strategy is urgently needed as a cost-effective and non-invasive diagnostic tool. In this paper we review the demographic, biologic, genetic and technical aspects that affect plasma Aβ levels. Findings of cross-sectional and longitudinal studies of plasma Aβ, including autosomal dominant AD cases, sporadic AD cases, Down syndrome cases and population studies, are also discussed. Finally, we review the association between cerebrovascular disease and Aβ plasma levels and the responses observed in clinical trials. Based on our review of the current literature on plasma Aβ, we conclude that further clinical research and assay development are needed before measures of plasma Aβ can be interpreted so they can be applied as trait, risk or state biomarkers for AD.
    Alzheimer's Research and Therapy 03/2013; 5(2):8. DOI:10.1186/alzrt162 · 3.98 Impact Factor
  • Source
    • "In the current study, plasma Aβ40 and Aβ42 were increased ~1.6 fold in DS as compared to non-DS subjects, which is slightly higher than would be predicted based on a gene dosage effect of APP but is lower than previous publications [14] [17]. However, plasma Aβ levels and ratios are not linearly associated with age in DS nor are they decreased in DS with AD, which contrasts with our observations in a group of patients with sporadic AD and a previous report in DS [22] [34].. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Adults with Down syndrome (DS) are at risk for developing Alzheimer's disease (AD). While plasma amyloid-β (Aβ) is known to be elevated in DS, its relationship to cognitive functioning is unknown. To assess this relationship, samples from two groups of subjects were used. In the first group, nondemented adults with DS were compared to: 1) a group of young and old individuals without DS and 2) to a group of patients with AD. Compared to these controls, there were significantly higher levels of plasma Aβ in nondemented adults with DS while AD patients showed lower levels of plasma Aβ. A larger second group included demented and nondemented adults with DS, in order to test the hypothesis that plasma Aβ may vary as a function of dementia and Apolipoprotein E (ApoE) genotype. Plasma Aβ levels alone did not dissociate DS adults with and without dementia. However, in demented adults with DS, ApoE4 was associated with higher Aβ40 but not Aβ42. After controlling for level of intellectual disability (mild, moderate, severe) and the presence or absence of dementia, there was an improved prediction of neuropsychological scores by plasma Aβ. In summary, plasma Aβ can help predict cognitive function in adults with DS independently of the presence or absence of dementia.
    Journal of Alzheimer's disease: JAD 01/2011; 23(3):399-409. DOI:10.3233/JAD-2010-101335 · 4.15 Impact Factor
Show more


6 Reads
Available from