engleski

Cerebrospinal fluid and genetic biomarkers in early detection of Alzheimer’s disease

Early diagnosis of Alzheimer’s disease (AD) in asymptomatic individuals is crucial because potential therapeutics should be administrated as early as possible, when neurodegeneration is not yet advanced. In this study we assessed whether the diagnostic potential of cerebrospinal fluid (CSF) biomarkers amyloid β 1-42 (Aβ1-42), total tau (t-tau), tau phosphorylated at epitope 181 (p-tau181), epitope 199 (p-tau199), epitope 231(p-tau231) and visinin-like protein 1 (VILIP-1) could be improved by genetic biomarkers related to serotonin metabolism (5-HT2A, 5-HT1B, 5-HT2C, and MAOB), inflammatory pathways (IL1α, IL1β, IL10, IL6, and TNFα), catecholamine metabolism (COMT, DBH), and survival of neurons (BDNF). We compared levels of Aβ1-42, t-tau, p-tau181, p-tau199, p-tau231, and VILIP-1 between patients with different DBH (rs1611115), IL1α (rs1800587), IL1β (rs1143623), IL6 (rs1800795), IL10 (rs1800896), TNFα (rs1800629), 5-HT2A (rs6313), 5-HT1B (re13212041), 5-HT2C (rs3813929), COMT(rs4680), BDNF (rs6265), and MAOB (rs1799836) genotypes. The study was conducted on 115 AD and 53 mild cognitive impairment (MCI) patients, 10 healthy controls and 56 patients with other causes of dementia (14 with vascular dementia [VaD], 23 with frontotemporal dementia, 7 with dementia with Lewy bodies, 3 with AD + VaD, 1 with corticobasal degeneration, 1 with hydrocephalus, 2 with Parkinson’s disease, 1 with epilepsy, and 4 with unspecified dementia). Levels of t-tau, p-tau181, p-tau199, p-tau231 and VILIP-1 were significantly higher in subjects with AA compared to GG and AG TNFα genotype (in patients with other dementias and in AD patients). Levels of p-tau199 and p-tau231 were significantly higher in patients with other dementias with CG compared to CC IL1β genotype. Levels of t-tau, p-tau181 and p-tau231 were significantly higher in patients with other dementias with AA compared to AG COMT genotype, while levels of Aβ1-42 were significantly lower in AD patients with GG compared to AG COMT genotype. Levels of p-tau181 were significantly higher in patients with other dementias with TT compared to CC and TC IL10 genotype, while levels of p-tau199 and p-tau231 were significantly higher in AD patients with CC compared to TC IL10 genotype. Levels of VILIP-1 were significantly higher in MCI patients with GC compared to GG IL6 genotype, while levels of p-tau199 were significantly higher in MCI patients and levels of t-tau were significantly higher inpatients with other dementias with GC compared to CC IL6 genotype. Levels of p-tau181 were significantly higher in AD patients with GA compared to AA and GG BDNF genotype and in MCI patients with CT compared to CC DBH genotype. Levels of Aβ1-42 were significantly lower in MCI patients with AA compared to GG MAOB genotype. The potential of NFα (rs1800629), IL1β(rs1143623), COMT(rs4680), IL10 (rs1800896), IL6 (rs1800795), BDNF(rs6265), DBH(rs1611115) and MAOB (rs1799836) polymorphisms in early diagnosis of AD should be tested further and validated on larger cohorts of patients.

Alzheimer's disease ; mild cognitive impairment ; cerebrospinal fluid ; biomarkers ; polymorphism ; serotonin metabolism ; inflammatory pathways ; catecholamine metabolism ; survival of neurons ; genetic susceptibility

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