These results highlight DS as a model to understand the role of APOE4 allele in unsuccessful ageing considering that a number of proinflammatory supernumerary genes (Cu/Zn superoxide dismutase, Ets-2 transcription factors, Down syndrome critical region 1, stress-inducible factor, interferon-alpha receptor and the amyloid precursor protein) are located on chromosome 21 and are implied in the pathologic processes of DS.
These results highlight DS as a model to understand the role of APOE4 allele in unsuccessful ageing considering that a number of proinflammatory supernumerary genes (Cu/Zn superoxide dismutase, Ets-2 transcription factors, Down syndrome critical region 1, stress-inducible factor, interferon-alpha receptor and the amyloid precursor protein) are located on chromosome 21 and are implied in the pathologic processes of DS.
We tested for association with loci previously associated with Alzheimer's disease risk and, despite the small size of the study, we detected associations with age at onset of Alzheimer's disease in Down syndrome with PICALM (β = 3.31, p = 0.011) and the APOE loci (β = 3.58, p = 0.014).
To investigate the relation of plasma levels of Abeta peptides (Abeta1-40 and Abeta1-42) and apolipoprotein E (APOE) genotype to dementia status, and the duration of Alzheimer's disease (AD) in adults with Down syndrome (DS).
The observed apoE allele epsilon 3 frequencies among patients with Down syndrome and healthy control subjects may help explain and support previous work that did not find high rates of atherosclerosis among these persons.
Haplotype analysis showed that individuals with Tau H1/H1 and ApoEɛ4 genotypes were more prevalent among DS participants with an earlier diagnosis of dementia (17%) compared to H1/H2 haplotypes (6%).
In Alzheimer's disease (AD), endosome abnormalities are among the earliest neuropathologic features to develop and have now been closely linked to genetic risk factors for AD, including APP triplication in Trisomy 21 (Down syndrome, DS) and ApoE4 genotype in sporadic AD.
Because the apolipoprotein E (ApoE) E4 allele is a risk factor for AD and possibly also for dementia of the AD type in DS, DNA samples were also ApoE genotyped.
Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer's disease and Down syndrome: differential effects of APOE genotype and presenilin mutations.
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.
Inheritance of the apolipoprotein E (ApoE) epsilon 4 allele is a risk factor for Alzheimer's disease (AD) and is associated with increased deposition of beta-amyloid (A beta) in AD, Down's syndrome, and normal aging.
As expected, the most strongly associated SNP was the APOE ɛ4rs429358 variant (HR=2.47 [1.58, 3.87], p=7.52×10(-5)), although variants within the more recently implicated SORL1 and RUNX1 genes were also strongly associated with DAD in DS (HR=0.54 [0.37, 0.80], p=0.002 and HR=1.61 [1.15, 2.26], p=0.006 respectively).
Compared with those with an apoE 3/3 genotype, the group of adults with DS with apoE 2/4, 3/4, and 4/4 genotypes were 5 times more likely to become demented (RR = 4.7; 95% CI = 1.2, 17.9).