Using the polymerase chain reaction, we analyzed the segregation of the ACT and ApoE polymorphisms in familial Alzheimer's disease (FAD) patients carrying mutations in Presenilin (PS) and APP genes and in both early onset (EO) and late onset (LO) FAD patients without known mutations.
In this study, we generated amyloid precursor protein/apoE knockout (APP/apoE<sup>KO</sup>) and APP/glial fibrillary acidic protein (GFAP)-apoE<sup>KO</sup> mice (the AD mice model used in this study was based on the APP-familial Alzheimer disease overexpression) to investigate the role of apoE, derived from astrocytes, in AD pathology and cognitive function.
Our findings of increased fMRI activation associated with APOE genotype but not with FAD mutations suggest that APOE exerts an effect on the BOLD signal that is not readily explained as a compensatory phenomenon.
EFAD mice are a well-characterized mouse model that express human APOE3 (E3FAD) or APOE4 (E4FAD) and overproduce human Aβ42 via expression of 5 Familial Alzheimer's disease (5xFAD) mutations.
Protein levels were compared between FAD mutation carriers (MCs) and noncarriers (NCs) and among APOE genotype groups, using multiple linear regression models.
Recent genome-wide scanning studies have revealed the existence of a new locus on chromosome 12, which, together with inheritance of the epsilon4 allele of apolipoprotein E gene, on chromosome 19, represent the most important genetic factors associated with an increased risk of developing the disease in late onset FAD families.
Recent findings suggest that the presence of APOE 4 is associated with an increased risk for both familial Alzheimer's disease and late-onset Alzheimer's disease.
In none of the FAD families analysed was there a significant effect of the ApoE genotype on the age of onset with the exception of one of the two mutated EOFAD families in which the epsilon 2 allele delayed the age of onset.
We performed genome-wide linkage and identity-by-descent (IBD) analyses on 41 non-Hispanic white families exhibiting likely dominant inheritance of LOAD, and having no mutations at known familial Alzheimer's disease (AD) loci, and a low burden of APOE ε4 alleles.
Besides familial Alzheimer's disease (AD), the genetic susceptibility has also been found in sporadic cases of AD, mostly related to the apolipoprotein E polymorphism.
This paper further reviews the mechanisms associated with AD causation for APOE and other candidate genes and implications for the development of prevention strategies.
Apolipoprotein E and GFAP showed negative regional association with amyloid-β (especially amyloid-β₄₀) accumulation in both sporadic and familial Alzheimer's disease.
The epsilon4 allele, a variant of the apolipoprotein E (ApoE) gene, is the most prominent genetic risk factor for sporadic, non-familial Alzheimer's disease (AD) currently known.