The overlap between Alzheimer's disease and epilepsy uncovered by transcriptome sequencing.
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ABSTRACT:
SUBMITTER: Jiang X
PROVIDER: S-EPMC7507445 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
Publications
The overlap between Alzheimer's disease and epilepsy uncovered by transcriptome sequencing.
Jiang Xiaowen X Lu Hongyuan H Liu Wenwu W Wu Zhongchan Z Wu Qiong Q Li Xiang X Xu Zihua Z Hui Fuhai F Zhao Qingchun Q
Clinical and translational medicine 20200901 5
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE6771: Temporal Cortex Control (mesial temporal lobe epilepsy control) GSE6773: Temporal neocortex mesial temporal lobe epilepsy GSE6774: Temporal Cortex Control (Alzheimer's disease control) GSE6775: Temporal Cortex Alzheimer's Disease GSE6777: Cerebellum Alzheimer's Disease GSE6778: Cerebellum Control (Alzheimer's disease control) Keywords: SuperSeries Refer to individual Series
2007-01-23 | E-GEOD-6834 | biostudies-arrayexpress
Project description:We investigated the genetic overlap between Alzheimer's disease (AD) and Parkinson's disease (PD). Using summary statistics (P-values) from large recent genome-wide association studies (GWAS) (total n=89 904 individuals), we sought to identify single nucleotide polymorphisms (SNPs) associating with both AD and PD. We found and replicated association of both AD and PD with the A allele of rs393152 within the extended MAPT region on chromosome 17 (meta analysis P-value across five independent AD cohorts=1.65 × 10(-7)). In independent datasets, we found a dose-dependent effect of the A allele of rs393152 on intra-cerebral MAPT transcript levels and volume loss within the entorhinal cortex and hippocampus. Our findings identify the tau-associated MAPT locus as a site of genetic overlap between AD and PD, and extending prior work, we show that the MAPT region increases risk of Alzheimer's neurodegeneration.
| S-EPMC4539304 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2007-01-23 | GSE6834 | GEO
Project description:Alzheimer's disease (AD) is a common cause of dementia with a strong genetic component and risk sharply increasing with age. We performed two parallel microarray experiments to independently identify genes involved in normal aging and genes involved in AD using RNA extracted from the temporal lobe of 22 late onset AD and 23 control brain donors. We found that AD is accompanied by significant changes in the expression of many genes with upregulation of genes involved in inflammation and in transcription regulation and downregulation of genes involved in neuronal functions. The changes with healthy aging involved multiple genes but were not as strong. Replicating and strengthening previous reports, we find a highly significant overlap between genes changing expression with age and those changing in AD, and we observe that those changes are most often in the same direction. This result supports an overlap between the biological processes of normal aging and susceptibility to AD and suggests that age related genes expression changes might increase the risk of developing AD.
| S-EPMC2945399 | biostudies-literature
Project description:Background: Alzheimer's disease (AD) and depression are debilitating brain disorders that are often comorbid. Shared brain mechanisms have been implicated, yet findings are inconsistent, reflecting the complexity of the underlying pathophysiology. As both disorders are (partly) heritable, characterising their genetic overlap may provide aetiological clues. While previous studies have indicated negligible genetic correlations, this study aims to expose the genetic overlap that may remain hidden due to mixed directions of effects. Methods: We applied Gaussian mixture modelling, through MiXeR, and conjunctional false discovery rate (cFDR) analysis, through pleioFDR, to genome-wide association study (GWAS) summary statistics of AD (n = 79,145) and depression (n = 450,619). The effects of identified overlapping loci on AD and depression were tested in 403,029 participants of the UK Biobank (UKB) (mean age 57.21, 52.0% female), and mapped onto brain morphology in 30,699 individuals with brain MRI data. Results: MiXer estimated 98 causal genetic variants overlapping between the 2 disorders, with 0.44 concordant directions of effects. Through pleioFDR, we identified a SNP in the TMEM106B gene, which was significantly associated with AD (B = -0.002, p = 9.1 × 10-4) and depression (B = 0.007, p = 3.2 × 10-9) in the UKB. This SNP was also associated with several regions of the corpus callosum volume anterior (B > 0.024, p < 8.6 × 10-4), third ventricle volume ventricle (B = -0.025, p = 5.0 × 10-6), and inferior temporal gyrus surface area (B = 0.017, p = 5.3 × 10-4). Discussion: Our results indicate there is substantial genetic overlap, with mixed directions of effects, between AD and depression. These findings illustrate the value of biostatistical tools that capture such overlap, providing insight into the genetic architectures of these disorders.
| S-EPMC8288283 | biostudies-literature
Project description:Most neurodegenerative disorders take decades to develop, and their early detection is challenged by confounding non-pathological ageing processes. Therefore, the discovery of genes and molecular pathways in both peripheral and brain tissues that are highly predictive of disease evolution is necessary. To find genes that influence Alzheimer's disease (AD) and Parkinson's disease (PD) pathogenesis, human RNA-Seq transcriptomic data from Brodmann Area 9 (BA9) of the dorsolateral prefrontal cortex (DLPFC), whole blood (WB), and peripheral blood mononuclear cells (PBMC) were analysed using a combination of differential gene expression and a random forest-based machine learning algorithm. The results suggest that there is little overlap between PD and AD, and the AD brain signature is unique mainly compared to blood-based samples. Moreover, the AD-BA9 was characterised by changes in 'nervous system development' with Myocyte-specific enhancer factor 2C (Mef2C), encoding a transcription factor that induces microglia activation, a prominent feature. The peripheral AD transcriptome was associated with alterations in 'viral process', and FYN, which has been previously shown to link amyloid-beta and tau, was the prominent feature. However, in the absence of any overlap with the central transcriptome, it is unclear whether peripheral FYN levels reflect AD severity or progression. In PD, central and peripheral signatures are characterised by anomalies in 'exocytosis' and specific genes related to the SNARE complex, including Vesicle-associated membrane protein 2 (VAMP2), Syntaxin 1A (STX1A), and p21-activated kinase 1 (PAK1). This is consistent with our current understanding of the physiological role of alpha-synuclein and how alpha-synuclein oligomers compromise vesicle docking and neurotransmission. Overall, the results describe distinct disease-specific pathomechanisms, both within the brain and peripherally, for the two most common neurodegenerative disorders.
| S-EPMC9104085 | biostudies-literature
Project description:BackgroundBlood plasma proteins have been associated with Alzheimer's disease (AD), but understanding which proteins are on the causal pathway remains challenging.ObjectiveInvestigate the genetic overlap between candidate proteins and AD using polygenic risk scores (PRS) and interrogate their causal relationship using bi-directional Mendelian randomization (MR).MethodsFollowing a literature review, 31 proteins were selected for PRS analysis. PRS were constructed for prioritized proteins with and without the apolipoprotein E region (APOE+/-PRS) and tested for association with AD status across three cohorts (n = 6,244). An AD PRS was also tested for association with protein levels in one cohort (n = 410). Proteins showing association with AD were taken forward for MR.ResultsFor APOE ɛ3, apolipoprotein B-100, and C-reactive protein (CRP), protein APOE+ PRS were associated with AD below Bonferroni significance (pBonf, p < 0.00017). No protein APOE- PRS or AD PRS (APOE+/-) passed pBonf. However, vitamin D-binding protein (protein PRS APOE-, p = 0.009) and insulin-like growth factor-binding protein 2 (AD APOE- PRS p = 0.025, protein APOE- PRS p = 0.045) displayed suggestive signals and were selected for MR. In bi-directional MR, none of the five proteins demonstrated a causal association (p < 0.05) in either direction.ConclusionApolipoproteins and CRP PRS are associated with AD and provide a genetic signal linked to a specific, accessible risk factor. While evidence of causality was limited, this study was conducted in a moderate sample size and provides a framework for larger samples with greater statistical power.
| S-EPMC8609677 | biostudies-literature
Project description:There is a substantial body of evidence that spontaneous recurrent seizures occur in a subset of patients with Alzheimer disease (AD), especially the familial forms that have an early onset. In transgenic mice that simulate these genetic forms of AD, seizures or reduced seizure threshold have also been reported. Mechanisms underlying the seizures or reduced seizure threshold in these mice are not yet clear and are likely to be complex, because the synthesis of amyloid β (Aβ) involves many peptides and proteases that influence excitability. Based on transgenic mouse models of AD where Aβ and its precursor are elevated, it has been suggested that seizures are caused by the downregulation of the Nav1.1 sodium channel in a subset of GABAergic interneurons, leading to a reduction in GABAergic inhibition. Another mechanism of hyperexcitability appears to involve tau, because deletion of tau reduces seizures in some of the same transgenic mouse models of AD. Therefore, altered excitability may be as much a characteristic of AD as plaques and tangles-especially for the familial forms of AD.
| S-EPMC3482723 | biostudies-other
Project description:Lead isotope analysis has been used to provenance metals such as lead, silver and bronze for many decades. Different approaches to interpret lead isotope ratios were proposed, and various limitations of the method have been discussed and addressed. Overlap in composition between different possible ore sources is always mentioned as a major limitation in lead isotope studies. However, it has never been comprehensively studied using a multivariate statistical approach. In this paper, the kernel density estimation (KDE) approach previously proposed by the authors is applied to calculate overlap between possible ore source regions. Firstly, the copper and lead ores of the same regions are compared, to assess if they are consistent and thus can be combined to increase sample size for provenance studies. Secondly, the pair-wise overlap between all the mining regions is calculated to determine if the distinction can actually be made between those ore fields. The use of one-dimensional KDE's is very effective for calculation and assessment of the overlap between ore sources. This study argues that merging the lead and copper ore data might increase the reliability of a region's KDE's in most cases, but the overlap should be assessed beforehand. Furthermore, the study provides useful tools to verify for every pair of possible ore sources if it is theoretically possible to discriminate between them, and to what extent.
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Project description: Not available
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