Genome-wide association and interaction studies of CSF T-tau/Aβ42 ratio in ADNI cohort

Li, Jin; Zhang, Qiushi; Chen, Feng; Meng, Xianglian; Liu, Wenjie; Chen, Dandan; Yan, Jingwen; Kim, Sungeun; Wang, Lei; Feng, Weixing; Saykin, Andrew J.; Liang, Hong; Shen, Li

doi:10.1016/j.neurobiolaging.2017.05.007

Cited by 29 publications

(20 citation statements)

References 40 publications

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“…In this respect, AD presents a decrease of CSF amyloid-ß 42 (Aß 42 ) burden and an increase in cerebrospinal fluid total tau (T-tau). Genome-wide association study (GWAS) and interaction study of T-tau/Aß 42 robustly replicated previously reported AD-related genes APOE4, APOC1, and TOMM40 and suggested other influencing factors, warranting future investigation [11]. Focusing on phosphorylated tau, GWAS identified a panel of five SNPs, rs6766238, rs1143960, rs1249963, rs11975968, and rs4836493, that are predictive for p-tau181/Aβ1-42 ratio (high/low), suggesting a panel of SNPs as a potential prognostic biomarker in ApoE4-negative MCI patients [12].…”

supporting

confidence: 66%

Specific protein biomarker patterns for Alzheimer’s disease: improved diagnostics in progress

Gozes

2017

EPMA Journal

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This short review looks at Alzheimer's disease (AD) diagnosis through my own point of view, going from imaging through cerebrospinal fluid to blood proteins. Over the last couple of years, we have published two papers targeted at Alzheimer's diagnosis. In one paper, we took an approach of selecting a specific target, namely, activitydependent neuroprotective protein (ADNP), and our results tightened the association of ADNP blood expression with intelligence. In another paper, we took an unbiased approach of analysis of all genes expressed in lymphoblastoid cells lines and discovered changes in expression of the regulator of G-protein signaling 2 (RGS2) as a potential AD predictor. This review will assess our data in comparison to selected independent studies focusing on blood protein biomarkers as well as assessing saliva and urine samples with potential predictive value for AD. Furthermore, the review will provide directions for a combination of innovative markers, stratifying the population toward disease prevention and personalized medicine.

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confidence: 66%

Specific protein biomarker patterns for Alzheimer’s disease: improved diagnostics in progress

Gozes

2017

EPMA Journal

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“…Table 1 shows the SNPs with FDR < 0.05 from the QTL analysis of Aβ 42 , T-tau/Aβ 42 ratio, p-tau/Aβ 42 ratio and ADAS13, respectively. A total of five SNPs were identified according to the threshold FDR < 0.05, and they were also reported by previous studies ( Li et al, 2017 ). Detected SNPs rs2075650, rs157580 and rs157582 are located within gene TOMM40.…”

Section: Resultsmentioning

confidence: 99%

Genome-Wide Association and Mechanistic Studies Indicate That Immune Response Contributes to Alzheimer’s Disease Development

et al. 2018

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Alzheimer’s disease (AD) is the most common cause of dementia. Although genome-wide association study (GWAS) have reported hundreds of single-nucleotide polymorphisms (SNPs) and genes linked to AD, the mechanisms about how these SNPs modulate the development of AD remain largely unknown. In this study, we performed GWAS for three traits in cerebrospinal fluid (CSF) and one clinical trait in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Our analysis identified five most significant AD related SNPs (FDR < 0.05) within or proximal to APOE, APOC1, and TOMM40. One of the SNPs was co-inherited with APOE allele 4, which is the most important genetic risk factor for AD. Three of the five SNPs were located in promoter or enhancer regions, and transcription factor (TF) binding affinity calculations showed dramatic changes (| Log2FC| > 2) of three TFs (PLAG1, RREB1, and ZBTB33) for two motifs containing SNPs rs2075650 and rs157580. In addition, our GWAS showed that both rs2075650 and rs157580 were significantly associated with the poliovirus receptor-related 2 (PVRL2) gene (FDR < 0.25), which is involved in spreading of herpes simplex virus (HSV). The altered regulation of PVRL2 may increase the susceptibility AD patients to HSV and other virus infections of the brain. Our work suggests that AD is a type of immune disorder driven by viral or microbial infections of the brain during aging.

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“…This promotes studies on very large cohorts e.g. (Adhikari et al, 2018), the development of reference databases (see for Alzheimer disease (Li et al, 2017), Parkinson disease (Chahine et al, 2018) or Human connectome project (Hodge et al, 2016)) and fair and robust comparison of image processing solutions (Commowick et al, 2018). Here, we propose to use the extension of the SHANOIR environment (Barillot et al, 2016) for storing preclinical imaging data, coupled with the VIP architecture for the dedicated image processing pipelines execution (Glatard et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

A Multicenter Preclinical MRI Study: Definition of Rat Brain Relaxometry Reference Maps

Deruelle¹,

Kober

Perles-Barbacaru

et al. 2020

Preprint

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Similarly to human population imaging, there are several well-founded motivations for animal population imaging, the most notable being the improvement of the validity of statistical results by pooling a sufficient number of animal data provided by different imaging centers. In this paper, we demonstrate the feasibility of such a multicenter animal study, sharing raw data from forty rats and processing pipelines between four imaging centers. As specific use case, we considered the estimation of T1 and T2 maps for the healthy rat brain at 7T. We quantitatively report about the variability observed across two data provider centers and evaluate the influence of image processing steps on the final maps, by using three fitting algorithms from three centers.Finally, to derive relaxation time values per brain area, two multi-atlas segmentation pipelines from different centers were executed on two different platforms. In this study, the impact of the acquisition was 2.21% (not significant) and 9.52% on T1 and T2 estimates while the impact of the data processing pipeline was not significant (1.04% and 3.33%, respectively). In addition, the computed normality values can serve as relaxometry reference maps to explore differences to animal models of pathologies.

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Genome-wide association and interaction studies of CSF T-tau/Aβ42 ratio in ADNI cohort

Cited by 29 publications

References 40 publications

Specific protein biomarker patterns for Alzheimer’s disease: improved diagnostics in progress

Specific protein biomarker patterns for Alzheimer’s disease: improved diagnostics in progress

Genome-Wide Association and Mechanistic Studies Indicate That Immune Response Contributes to Alzheimer’s Disease Development

A Multicenter Preclinical MRI Study: Definition of Rat Brain Relaxometry Reference Maps

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