Genetic mutations of APOEε4 carriers in cardiovascular patients lead to the development of insulin resistance and risk of Alzheimer's disease

Abstract

Type 2 diabetes mellitus and Alzheimer's disease (AD), both are chronic and progressive diseases. Many cardiovascular and genetic risk factors are considered responsible for the development of AD and diabetes mellitus (DM). Genetic risk factor such as apolipoprotein E (APOE) plays a critical role in the progression of AD.Specifically, APOEε4 is genetically the strongest isoform associated with neuronal insulin deficiency, altered lipid homeostasis, and metabolism, decreased glucose uptake, impaired gray matter volume, and cerebrovascular functions. In this article, we have summarized the mechanisms of cardiovascular disturbances associated with AD and DM, impact of amyloid-β aggregation, and neurofibrillary tangles formation in AD. Moreover, cardiovascular risk factors leading to insulin resistance (IR) and amyloid-β aggregation are highlighted along with the effects of APOE risk alleles on cerebral, lipid, and cholesterol metabolism leading to CVD-mediated IR. Correspondingly, the contribution of IR, genetic and cardiovascular risk factors in amyloidβ aggregation, which may lead to the late onset of AD and DM, has been also discussed. In short, IR is related to significantly lower cerebral glucose metabolism, which sequentially forecasts poorer memory performance. Hence, there will be more chances for neural glucose intolerance and impairment of cognitive function in cardiac patients, particularly APOEε4 carriers having IR. Hence, this review provides a better understanding of the corresponding crosstalk among different pathways.This will help to investigate the rational application of preventive measures against IR and cognitive dysfunction, specifically in APOEε4 carriers' cardio-metabolic patients.

Knowledge about hypertension and associated factors among patients with hypertension in public health facilities of Gondar city, Northwest Ethiopia: Ordinal logistic regression analysis

“…Hypertension is a disease that imposes risks of diseases on other systems including on CNS (Central Nervous system), renal system and CVS (Cardiovascular diseases) [1]. Various cardiovascular risk factors have been identified to be a cause of the acquisition of Alzheimer's disease by affecting the metabolism of cerebral glucose this eventually leads to memory loss and development of diabetes mellitus by causing insulin resistance [2]. Whereas raised Blood Pressure (BP) is among the key risk factors of non-communicable diseases (NCD).…”

A Review of ApoE4 Interference Targeting Mitophagy Molecular Pathways for Alzheimer's Disease

“…Other rising insights draw more and more interests broadly. The existing investigation of APOE ε4 pathogenesis in AD (Norwitz et al, 2021 ; Serrano-Pozo et al, 2021 ) has expanded beyond Aβ peptide-centric mechanisms to Tau neurofibrillary degeneration, neuroinflammation (Kaur et al, 2019 ; Leng and Edison, 2021 ), synaptic loss (Zhao et al, 2020 ), depression (Rhodes et al, 2021 ; Zhang et al, 2021 ), blood–brain barrier disruption (Rhea and Banks, 2021 ; Zhang and Xie, 2021 ), insulin resistance (Jabeen et al, 2021 ), gut dysfunction (Hoffman et al, 2019 ), oxidative stress (Butterfield and Mattson, 2020 ), and autophagic deficit (Chen et al, 2021 ; Sohn et al, 2021 ; Eran and Ronit, 2022 ); particularly, damaged mitophagy (Simonovitch et al, 2019 ; Schmukler et al, 2020 ; Liang et al, 2021a ; Morton et al, 2021 ; Wang et al, 2021b ). However, the precise molecular mechanisms underlying ApoE4 pathogenic effects during AD have not yet been elucidated.…”

Analysis of mRNA-miRNA-lncRNA differential expression in prediabetes/type 2 diabetes mellitus patients as potential players in insulin resistance

“…Insulin resistance has been identified as a leading cause of major health problems such as diabetes, hyperlipidemia, hypertension, and cardiovascular disease ( 1 , 2 ). Insulin resistance can begin years before type 2 diabetes mellitus is diagnosed, even before prediabetes is recognized ( 3 ).…”