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.
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.
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.
Apolipoprotein E and GFAP showed negative regional association with amyloid-β (especially amyloid-β₄₀) accumulation in both sporadic and familial Alzheimer's disease.
Protein levels were compared between FAD mutation carriers (MCs) and noncarriers (NCs) and among APOE genotype groups, using multiple linear regression models.
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.
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.
This study reports correlation of the hippocampal neurofibrillary tangles (NFT) density with beta-amyloid (Abeta) precursor protein (APP) 717 mutation, presenilin (PS)-1 mutation and apolipoprotein E (Apo-E) e4 alleles (E4), being graded as 3 forms (no-E4, one-E4 and two-E4) in autopsied brains from patients with familial and non-familial Alzheimer's disease (AD).
This paper further reviews the mechanisms associated with AD causation for APOE and other candidate genes and implications for the development of prevention strategies.
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.