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%).
Further research should include a large sample of adults with DS selected on diagnosed painful conditions to obtain more insight into the possible role of ApoE genotype (and its association with cognition) in the pain experience of this target group.
APOE4 is a major genetic risk factor for Alzheimer disease and is associated with dementia in Down syndrome and poor neurological outcome after traumatic brain injury, cerebral hemorrhage, and other neuropathological disorders.
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).
APOE4 is a major genetic risk factor for Alzheimer's disease and is associated with Down's syndrome dementia and poor neurological outcome after traumatic brain injury and haemorrhage.
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).
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).
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.
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.
Our findings suggest that the -850T allele, which is more common among patients at high risk of dementia such as those with DS, might eventually play a role in the development of dementia; no inference on the role of the allele APOE E4 in DS-related dementia may be derived from our results.
As hepatitis B virus (HBV) infection and hypothyroidism also are common in DS, we evaluated associations between ApoE type, HBV status, and thyroid status in a sample of older persons with DS (n = 55; mean age, 44.3 +/- 10.8 years) using chi-squared analysis.
Allele varepsilon4 of apolipoprotein E gene is less frequent in Down syndrome patient of the Sicilian population and has no influence on the grade of mental retardation.
Plasma levels of Abeta 40 and 42 did not correlate with apoE genotypes in DS and control cases, and with the extent of mental retardation in DS subjects.
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.
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.