Hypomethylation of CpGs in BIN1 might play an important role in the expression of BIN1 and may be a biomarker for identifying individuals at high risk of developing LOAD.
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.
Additional studies are needed to confirm the usefulness of BACE1, alone or in combination with other markers, in discriminating patients and predicting LOAD onset and progression.
Apolipoprotein (APOE) ɛ4 is a well-known risk factor for late-onset Alzheimer's disease (AD), but other AD-related gene polymorphisms might also be important, such as the polymorphism within the brain-derived neurotrophic factor (BDNF) gene.
We found evidence of late-onset Alzheimer disease (LOAD)-associated genetic polymorphism within an exon of Mucin 6 (MUC6) and immediately downstream from another gene: Adaptor Related Protein Complex 2 Subunit Alpha 2 (AP2A2).
In summary, polymorphism in a repeat-rich region near AP2A2 was associated with neocortical pTau proteinopathy (because of the unique repeats, prior genome-wide association studies were probably unable to detect this association), and AP2A2 was often colocalized with neurofibrillary tangles in LOAD.
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).
The odds ratios (ORs) with the respective 95% confidence interval (95%CI) were put to use for the evaluation of the robustness of the link of the MTHFRC677T polymorphism with the vulnerability to 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.
The triggering receptor expressed on myeloid cells 2 (TREM2) gene is associated with the pathogenesis of LOAD and plays important roles in mediating the phagocytosis of Aβ by microglia and regulating inflammation in central nervous system.