All patterns, except the superior parietal pattern, were influenced by apolipoprotein E. Our step-wise approach revealed atrophy patterns that partially resembled imaging findings in early stages of AD.
This suggests that APOE-ε4-related vascular factors are also part of the pathway to AD pathology, in synergy with an elevated immune response, and could become targets for trials focused on delaying AD.
In this study, we report that common single nucleotide polymorphism (SNP) variation in BACE2 is associated with altered AD risk in apolipoprotein E gene (APOE) epsilon 4 variant (ε4) non-carriers.
Genome-wide association studies indicate that the possession of two apoE4 alleles is a strong genetic risk factor for late-onset Alzheimer's disease (LOAD).
APOE, MTHFR A1298C and BDNF C270T polymorphisms may be associated with LOAD and BDNF and MTHFR alleles may play a role in the age at onset of the LOAD.
We identified 31 articles which suggested that APOE genotyping for LOAD susceptibility provides potential benefits to at-risk patients and can guide changes in positive health-related behaviors.
Late-onset Alzheimer's disease is multifactorial and associated with many different genetic risk loci (>20), with the apolipoprotein E ε4 allele being a major genetic risk factor for late-onset Alzheimer's disease.
Genetic studies indicate that most of the risk of developing late onset Alzheimer's disease, the most common form of the disease, affecting patients aged 65 years and older, is associated with genes (ie, APOE, APOJ, and SORL) that are mainly expressed by glial cells (ie, astrocytes, microglia, and oligodendrocytes).
A better understanding of apoE isoform-specific interaction with their metabolic receptor LRP1 on Aβ metabolism is crucial for defining APOE4-related risk for AD.
Apolipoprotein E (APOE) is a susceptibility gene for late-onset Alzheimer's disease neuropathology; less is known about the relationship between APOE and cerebrovascular disease (CVD) neuropathology.
Furthermore, in the subgroup analysis carried out using APOE ɛ4 status, a substantial increase in the susceptibility to LOAD was detected in APOE ɛ4 carriers as well as non-APOE ɛ4 carriers.
This review discusses recent advances in understanding the different functions of APOE in the periphery and in the brain, and highlights several promising APOE-targeted therapeutic strategies for AD.
To identify rare variants possibly explaining part of the genetic architecture for LOAD in Japanese people, we performed whole-exome sequencing analyses of 202 LOAD individuals without the APOE ε4 risk allele, a major genetic factor for LOAD susceptibility.
However, self-assembly of the ApoE4 isoform may play a role in pathogenesis, and these results open opportunities for uncovering new triggers for AD onset.
Collectively, these data identify a novel gene-regulatory pathway involving CXorf56 that may link apoE4 to microglia activation and inflammation associated with AD.
Altogether, these new knock-in strains offer a novel and dynamic tool to study the role of APOE in AD pathogenesis in a spatially and temporally controlled manner.
The gene APOE is associated with cognitive change and late-onset Alzheimer's disease, and epidemiological studies have provided strong evidence that the e<sub>2</sub> allele of APOE has a neuroprotective effect, it is associated with increased longevity and an extended healthy lifespan in centenarians.
In addition, the known LOAD risk factor, APOE was included in this study to test whether any BER gene variants associate with APOE variants, particularly APOE ε4.
Our results support apoE4-related early-life plasticity impairments that precede the AD clinical manifestations and affect any brain area that depends on extensive plasticity; early impairments that may promote the development of AD pathologies later in life.