Abstract
BackgroundGenetics play a significant role in the etiology of late-life neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease, and frontotemporal dementia. Part of the individual differences in risk for these diseases can be traced back decades before the onset of disease symptoms. Previous studies have shown evidence for plausible links of apolipoprotein E (APOE), the most important genetic marker for Alzheimer’s disease, with early-life cognition and neuroimaging markers. We aimed to assess whether genome-wide genetic burden for the aforementioned neurodegenerative diseases plays a role in early-life processes.MethodsWe studied children from the Generation R Study, a prospective birth cohort. APOE genotypes and polygenic genetic burdens for Alzheimer’s disease, Parkinson’s disease, and frontotemporal dementia were obtained through genome-wide genotyping. Non-verbal intelligence was assessed through cognitive tests at the research center around the age of 6 years, and educational attainment through a national school performance test around the age of 11 years. The Child Behavior Checklist was administered around the age of 10 years, and data from the anxious/depressed, withdrawn/depressed, and the internalizing behavior problems scales were used. Children participated in a neuroimaging study when they were 10 years old, in which structural brain metrics were obtained. Lipid serum profiles, which may be influenced by APOE genotype, were assessed from venal blood obtained around the age of 6 years. The sample size per analysis varied between 1,641 and 3,650 children due to completeness of data.ResultsWe did not find evidence that APOE genotype or the polygenic scores impact on childhood nonverbal intelligence, educational attainment, internalizing behavior, and global brain structural measures including total brain volume and whole brain fractional anisotropy (all p > 0.05). Carriership of the APOE ε2 allele was associated with lower and APOE ε4 with higher low-density lipoprotein cholesterol concentrations when compared to APOE ε3/ε3 carriers.ConclusionWe found no evidence that genetic burden for late-life neurodegenerative diseases associates with early-life cognition, internalizing behavior, or global brain structure.
Highlights
Genetic factors play a significant role in the etiology of late-life neurodegenerative diseases like Alzheimer’s disease (AD) [1, 2], Parkinson’s disease (PD) [3], and frontotemporal dementia (FTD) [4]
High-density lipoprotein cholesterol (HDL-c), and triglyceride concentrations were derived with the Roche cobas 8000 analyzer (Roche Diagnostics GmbH, Penzberg, Germany), and low-density lipoprotein cholesterol (LDL-c) was estimated using the Friedewald equation [48]. We considered these lipids in relation to apolipoprotein E (APOE) status and the AD polygenic risk scores (PGRS) as the APOE gene plays a significant role in lipid metabolism [49], whereas we did not have such a prior expectation for PD and FTD
None of the measures for genetic burden for AD, PD, or FTD were associated with childhood non-verbal intelligence quotient (IQ), educational attainment, internalizing behavior, global brain structure, or disease-specific regional brain structures
Summary
Genetic factors play a significant role in the etiology of late-life neurodegenerative diseases like Alzheimer’s disease (AD) [1, 2], Parkinson’s disease (PD) [3], and frontotemporal dementia (FTD) [4]. As APOE increases the risk for AD, its role in early-life cognition and brain markers has been studied. Genetics play a significant role in the etiology of late-life neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease, and frontotemporal dementia. Previous studies have shown evidence for plausible links of apolipoprotein E (APOE), the most important genetic marker for Alzheimer’s disease, with early-life cognition and neuroimaging markers. We aimed to assess whether genome-wide genetic burden for the aforementioned neurodegenerative diseases plays a role in early-life processes
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