APOE genetic variants and apoE, miR-107 and miR-650 levels in Alzheimer’s disease

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative dementia in adults. Pathogenesis of AD depends on various factors, including APOE genetic variants, apolipoprotein E (apoE) phenotype and oxidative stress, which may promote both DNA and RNA damage, including non-coding RNA (ncRNA). Among ncRNAs, microRNA (miRNA) is known to contribute to pathologic processes in AD. The aim of the study was to analyse the plasma concentration of apoE by ELISA as well as the plasma levels of miR-107 and miR-650 by qPCR in relation to APOE genetic variants and clinical features including the age of onset and dementia severity in 64 AD patients and 132 controls. Our data showed that a low apoE plasma concentration was a risk factor for developing AD (OR = 5.18, p = 6.58E-06) and was particularly pronounced in severe dementia (p < 0.001) and correlated with cognitive functions (R = 0.295, p = 0.020), similarly as the level of miR-650 (R = 0.385, p = 0.033). The presence of APOE E4 allele in both AD patients and controls led to a reduction in apoE, while APOE E3/E3 genotype was associated with an increased apoE concentration and level of miR-107 in AD (p < 0.05) which was inversely correlated with the number of APOE E4 alleles (R =-0.448, p = 0.009). Additionally, patients with the onset at 60-69 years of age showed a reduced level of miR-107 (p < 0.05, as compared to AD above 80 years of age). Changed levels of plasma apoE, miR-107 and miR-650 may be a marker of the neurodegenerative process in the course of AD, associated with amyloid β metabolism and inordinate cell cycle.

Expression and function of Ndel1 during the differentiation of neural stem cells induced by hippocampal exosomes

“…A growing body of evidence indicates that aberrant miR-107 expression plays a key role in cancers, including breast cancer (Luo et al, 2019), gastric cancer (Liu et al, 2018), cervical cancer (Zhou et al, 2014), hepatocellular carcinoma (Ali et al, 2019), and non-small cell lung cancer (Zhang et al, 2014). Prendecki et al indicated that altered miR-107 levels may be a marker of the neurodegenerative process during the course of AD, which is associated with amyloid β metabolism and excessive cell cycle progression (Prendecki et al, 2019). Our study found that miR-107-3p was highly expressed in nervous tissues; moreover, we found that Ndel1 was directly regulated by miR-107-3p.…”

Profiling Basal Forebrain Cholinergic Neurons Reveals a Molecular Basis for Vulnerability Within the Ts65Dn&nbsp;Model of Down Syndrome and Alzheimer’s Disease

“…The ApoE e4 isoform is known to drive AD pathology (106). Low plasma levels of ApoE were observed in subjects with severe dementia, correlating with cognitive decline (107). Increases in Capn1 activation have previously been linked to AD pathology (108,109).…”

The Synaptic Vesicle Protein 2a Interacts With Key Pathogenic Factors in Alzheimer’s Disease: Implications for Treatment

“…The depletion of BACE1, which initiates Aβ production by cleaving the extracellular domain of APP [47], has been reported to restore part of the synaptic function, indicating that BACE1 may be necessary for optimal synaptic activity and cognition [48]. APOE is a major risk factor for Alzheimer's disease (AD) [49]. Studies have shown that the level of BACE1 in the brain may be affected by APOE before the onset of AD [50,51].…”