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Alzheimer's disease (AD) is the most common form of dementia, generally affecting elderly people in the age group of above 60–65 years. Amyloid deposition has been found to be a possible cause and a characteristic feature of Alzheimer's disease. Mutations, variant genotypes, or downregulation that reduce amyloid clearance or accelerate amyloid accumulation can lead to Alzheimer's disease. This study involved clinically confirmed AD patients, age matched controls of similar ethnicity, and patients who had no history of cancer or any other chronic disease. DNA and RNA extractions of samples were done as per Saguna et al. [45] and TRIzol method, respectively. Frequencies of variant genotypes were observed using the RFLP technique, whereas, for expression analysis, qPCR was performed. The association between diet, smoking status, family history, and co-morbidities was calculated using statistical tools. Expression analysis showed downregulation in more than 65% of AD cases. Hypertension and diabetes also had a significant association with AD. Allelic isoforms ε2:ε2 and ε2:ε3 tend to be less frequent among AD cases compared to controls (2.85% vs 26.15% and 11.42% vs 21.43%, respectively). Among individuals (AD cases) with ε2:ε3 and ε2:ε4, 37.5% of the patients were having severe dementia and 62.5% were having mild to moderate dementia, whereas, among individuals with ε3:ε4 and ε4:ε4, 57% were having severe dementia and 43% were having mild to moderate dementia. Besides this, all early-onset Alzheimer's patients were found to have at least one ε4 allele. The percentage of individuals with family history (cases vs controls) was 34.17% vs 3.75%, without family history 64.55% vs 95%. On comparing AD cases against controls for smoking status, the results observed are the following: chain smokers, 12.65% vs 18.75%; moderate smokers, 16.45% vs 6.25%; ex-smokers, 36.70% vs 22.50%; non-smokers, 34.17% vs 52.50%. On comparing dietary habits in AD cases against controls, the results were as follows: individuals with generally fatty diet 26.58% vs 11.25%, with mixed diet 36.70% vs 78.75%, with generally vegetarian diet 34.17% vs 10.00%, data not available 2.53% among AD cases. Family history, dietary habits, genetics, and socioeconomic status are strongly associated with the development of Alzheimer disease. Although family history or genetic makeup cannot be changed, eating habits can be changed quite easily. We simply need to go from a high-fat diet to one that is lower in fat. Regarding socioeconomic status, which includes stress of both kinds, including economic stress, stress brought on by the loss of loved ones through death or separation, and co-morbidities (hypertension and diabetes), all are manageable and even modifiable through counseling, positive behavior, and physical activity like exercise, walking, cycling, and playing games. [ABSTRACT FROM AUTHOR]

To determine the functional connectome change pattern based on subregions of the hippocampus in young APOEε4 carriers during a 3-year follow-up. All the participants (n = 213) were tested for resting-state functional MRI, neuropsychological scales, and APOE genotype. The age- and sex-matched APOE ε4/ε3 (23.9 ± 3.2 years old, 6 female/7 male) carriers and APOE ε3/ε3 (22.9 ± 1.6 years old, 7 female/12 male) carriers were finally followed up. The hippocampus and its anterior/middle/posterior subregion-based functional connectivity (FC) patterns were compared between APOEε4 and APOEε3 groups by a two-sample t-test at baseline and mixed-effect analysis at follow-up. The effective connectivity (EC) patterns among the altered regions of interaction effect were examined in the APOEε4 groups. APOEε4 carries displayed saliently enhanced FC in the right anterior/middle hippocampus and core regions of the default mode network (DMN) (P < 0.05 by Gaussian Random Fields (GRF) correction). However, the APOEε4-by-time interaction was evident in the middle/posterior hippocampus with connection to the lateral temporal lobe and anterior cingulate cortex (ACC) (P < 0.05 by GRF correction). Moreover, the APOEε4 group at follow-up showed increased EC separately from both the left middle hippocampus and lateral temporal lobe to the left posterior hippocampus, and its changes of FC/EC significantly correlated with altered memory function. The posterior hippocampus might be especially vulnerable to early modulation in young APOEε4 carriers. Its connection with the lateral temporal lobe, rather than with DMN, might be the early compensative mechanism of memory function regulation influenced by APOE ε4 in the young adults. [ABSTRACT FROM AUTHOR]

Polymorphisms of the cholesterol-24S-hydroxylase (CYP46A1) and apolipoprotein E (APOE) genes are risk factors for Alzheimer’s disease (AD). Plasma level of 24S-hydroxcholesterol (24-OHC), the metabolite of cholesterol, is thought to correlate with AD. The present study investigated the correlation between these genetic factors and blood 24-OHC and amyloid-beta (Aβ) levels in AD patients. Association analysis, logistic regression, and linear regression were used to analyze the correlation of CYP46A1 and APOE genotypes with blood 24-OHC and Aβ levels and AD risk. We found that the APOEε4 alleles were significantly higher in patients with AD and there was a potential synergistic interaction between the CYP46A1 C allele and APOEε4 allele in AD. Blood 24-OHC level and Aβ level were significantly higher in AD patients than controls, indicating 24-OHC could be a marker in AD diagnosis. However, AD patients with the CYP46A1 TT, but not CC, genotype had higher 24-OHC levels, which indicated that there may be other mechanisms in the relationship between CYP46A1 polymorphisms and AD. [ABSTRACT FROM AUTHOR]