Association Studies of Specific Cholesterol Related Genes (APOE, LPL, and CETP) with Lipid Profile and Memory Function: A Correlative Study Among Rural and Tribal Population of Dharmapuri District, India

Abstract

Epidemiological studies state that dementia has multiple etiologies including genetic mutation, genetic variation, and environmental factors. Accumulating evidence suggests that dysregulation of cholesterol homeostasis is the major etiological factor in initiating neurodegeneration. Apolipoprotein E (APOE) polymorphic alleles and associated polymorphism of lipoprotein lipase (LPL) and cholesteryl ester transfer protein (CETP) that are important components in regulating cholesterol metabolism are implicated in neurodegenerative diseases. Therefore, the current study focused on identifying the association between several common polymorphism (viz., APOE, CETP, and LPL) to that of change in serum lipid levels and memory symptoms. Volunteer subjects aged 50 and above from rural and tribal areas of the Dharmapuri district, Tamilnadu, India were chosen for the current study and polymorphism was analyzed using PCR-RFLP. Fasting lipid profile and memory function using simplified version of Global Clinical Dementia rating were assessed. Significant difference in the major lipid profile parameters were observed (TC, TGL, LDL, VLDL) among rural and tribal populations that were associated with significant genotypic variation of APOE, CETP, and LPL. Regression analysis revealed significant risk for memory loss that are dependent on age and genetic variants like CETP. These data predict positive correlation between cholesterol-associated genes and their relationship to altered lipid profile and memory symptoms, which possibly link gene-polymorphism and susceptibility ratio for aging and dementia.

Involvement of Lipids in Alzheimer’s Disease Pathology and Potential Therapies

“…Depletion of lipid rafts decreased dendritic density and increased the synapse, disrupting neuronal communication (Martin, 2000;Hering et al, 2003;Sebastiao et al, 2013;Wang, 2014). The transport protein, apolipoprotein E (apoE), monitors cholesterol transport from glial cells to neurons, and impaired ApoE is implicated in deficits in synaptic plasticity and cognitive function (Periyasamy et al, 2017). Of the three isoforms of ApoE, ApoE4 is a prevalent risk factor that is synergistic with obesity and age for AD (Butler, 1994;Riedel et al, 2016;Jones and Rebeck, 2018;O'Donoghue et al, 2018;Glorioso et al, 2019).…”

Causal association of circulating cholesterol levels with dementia: a mendelian randomization meta-analysis

“…For the association between ApoE gene polymorphism ε2/ε3/ε4 and dementia, there were 27 studies with 3136 dementia patients and 3103 healthy controls [29][30][31][32][33][34][35][36][37][38][39][40][41] . For the association between ApoE gene ε2/ ε3/ε4 polymorphism and circulating cholesterol, five studies addressed HDL-C 35,[42][43][44][45] , five studies addressed LDL-C 35,[42][43][44][45] , seven studies addressed TG 35,[42][43][44][45][46][47] and six studies addressed TC 35,[42][43][44][45][46] , were included.…”

Resveratrol Mediated Regulation of Hippocampal Neuroregenerative Plasticity via SIRT1 Pathway in Synergy with Wnt Signaling: Neurotherapeutic Implications to Mitigate Memory Loss in Alzheimer’s Disease

“…Epidemiological data suggest that hypertension, cardiovascular diseases, hypercholesterolemia, diabetes, obesity, inflammation, and viral infections are the potential risk factors for the development of the sporadic form of AD [31,32]. Genotypic versions of the apolipoprotein E (ApoE) have also been considered as a principal diseasecausing molecular determinant of sporadic forms of AD, as they play a key role in the regulation of lipid metabolism [33]. Whereas the familial forms of AD are very rare and are linked to mutations in various genes involved in A␤PP processing [34].…”