β-catenin and GSK3 levels are pivotal in the neurodegeneration associated to AD contributing to memory deficits, tau phosphorylation, increased β-amyloid production and modulation of Apolipoprotein E in the brain.
[1997] reported a synergistic effect between the genes for BChE-K variant and apolipoprotein E (ApoE) epsilon 4, which increases the risk for late onset AD.
Yet, cross-sectional studies in normal older individuals show little evidence for an association between markers of AD risk (APOE4 genotype and amyloid deposition), and white matter integrity.
Yet CYP19 genetic variation did seem to contribute to AD development in women as the rs4646 genotypes carrying the T allele were associated with an earlier onset age (p = 0.01) independently of a similar effect determined by the APOE e*4 allele (p = 0.005).
Worsening of performance on a delayed word recall task (Alzheimer's Disease Assessment Scale cognitive subscale) showed an identical pattern in association with APOE*E4 allele dose and sex.
Worldwide evidence has recently shown that the allele epsilon4 of apolipoprotein E (ApoE) is a genetic risk factor for Alzheimer's disease (AD) underlining the possible role of apoE in the physiopathology of AD.
With respect to biomarkers, elderly nondemented APOE epsilon4 carriers demonstrated distinct cerebrospinal fluid biomarker signatures and alterations of brain glucose metabolism similar to those observed in AD.
Whole exome sequencing analysis of known disease-associated genes, copy number analysis, APOE ε genotyping and C9orf72 repeat expansion analysis were performed to identify defects in genes with a well-established involvement in Parkinson's disease or AD.
Whole brain volume was quantified by using high-resolution magnetic resonance imaging and the computerized brain segmentation technique in 178 patients with late-onset sporadic Alzheimer's disease who carried no APOE epsilon 4 alleles (N = 62), one epsilon 4 allele (N = 93), or two (N = 23) and had comparable clinical severity of dementia.
Whilst ApoE4 genotype (AUC = 0.737) and Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 13 (AUC = 0.724) independently discriminated amyloid-PET(+) and amyloid-PET(-) MCI individuals, the combination of clinical markers (ApoE4 carrier, age >60 years and ADAS-Cog 13 > 13.5) improved the predictive accuracy of amyloid-PET status (AUC = 0.827, P < 0.001).
While this may be related to increased brain amyloid load as a consequence of ApoE genotype, the possibility exists that ApoE may be a specific factor in vascular abnormalities associated with AD.
While the use of APOE genotyping has provided a method to identify individuals at greatest risk of Alzheimer disease, how other factors modify the degrees of the APOE-related risk needs to be further investigated.
While the evidence of an association between the apolipoprotein E (APOE) *E4 allele and Alzheimer's disease is very strong, the effect of the *E4 allele on cognitive decline in the general population is more equivocal.
While the CSF levels of A beta 42, apoE, and transthyretin are reported to be reduced in AD, we found no relationship between age, gene, or apoE phenotype and the level of any of these proteins in the CSF of nondemented individuals.
While the apolipoprotein E (ApoE) epsilon 4 allele is a recognized risk factor for Alzheimer's disease (AD), an association of epsilon 4 with other neurodegenerative diseases (NDs) has not been extensively explored.
While the APOE epsilon4 allele was strongly associated with AD risk in our series, we found no evidence for an interaction between the APOE and ACE loci.
While part of the association of the apoE polymorphism with AD is supposed to be caused by apoE-isoform dependent effects on amyloid-beta deposition, no single pathogenetically relevant mechanism has yet been confirmed for MS.
While most positive results were largely contradictory, we identified three loci-on chromosomes 6p21, 10q24, 11q23-that yielded positive results in three or more independent studies, in addition to the well-established AD association with the gene encoding apolipoprotein E (APOE).
While genetic testing for the apolipoprotein E (APOE) gene--a risk factor for sporadic AD--is widely debated, it may become necessary in the context of novel disease-modifying drugs.