Transcriptomic Downregulation of APOE, Polymorphic Variations of APOE, Diet, Social Isolation, and Co-morbidities as Contributing Factors to Alzheimer's Disease: a Case-Control Study of Kashmiri Population.

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.