AI Article Synopsis
- The study investigates how variations in the BIN1 gene are linked to neuroinflammation and Alzheimer's disease (AD) pathology, focusing on two specific genetic polymorphisms: rs7561528 and rs744373.
- Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Chinese Alzheimer's Biomarker and Lifestyle (CABLE) study, researchers found a significant relationship between BIN1 loci and levels of key Alzheimer's biomarkers in cerebrospinal fluid (CSF), particularly phosphorylated-tau (P-tau), total-tau (T-tau), and microglial activation marker sTREM2.
- The findings suggest that the association between BIN1 loci and tau pathology is
Article Abstract
Background: Bridging integrator 1 (BIN1) gene polymorphism has been reported to play a role in the pathological processes of Alzheimer's disease (AD).
Objective: To explore the association of BIN1 loci with neuroinflammation and AD pathology.
Methods: Alzheimer's Disease Neuroimaging Initiative (ADNI, N = 495) was the discovery cohort, and Chinese Alzheimer's Biomarker and LifestylE (CABLE, N = 619) study was used to replicate the results. Two BIN1 gene polymorphism (rs7561528 and rs744373) were included in the analysis. Multiple linear regression model and causal mediation analysis conducted through 10,000 bootstrapped iterations were used to examine the BIN1 loci relationship with cerebrospinal fluid (CSF) AD biomarkers and alternative biomarker of microglial activation microglia-soluble triggering receptor expressed on myeloid cells 2 (sTREM2).
Results: In ADNI database, we found a significant association between BIN1 loci (rs7561528 and rs744373) and levels of CSF phosphorylated-tau (P-tau) (pc = 0.017; 0.010, respectively) and total-tau (T-tau) (pc = 0.011; 0.013, respectively). The BIN1 loci were also correlated with CSF sTREM2 levels (pc = 0.010; 0.008, respectively). Mediation analysis demonstrated that CSF sTREM2 partially mediated the association of BIN1 loci with P-tau (Proportion of rs7561528 : 20.8%; Proportion of rs744373 : 24.8%) and T-tau (Proportion of rs7561528 : 36.5%; Proportion of rs744373 : 43.9%). The analysis in CABLE study replicated the mediation role of rs7561528.
Conclusions: This study demonstrated the correlation between BIN1 loci and CSF AD biomarkers as well as microglia biomarkers. Additionally, the link between BIN1 loci and tau pathology was partially mediated by CSF sTREM2.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.3233/JAD-240372 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Neuropathology-based approach reveals novel Alzheimer's Disease genes and highlights female-specific pathways and causal links to disrupted lipid metabolism: insights into a vicious cycle.
Acta Neuropathol Commun
January 2025
Department of Biological Sciences, Purdue University, 915 Mitch Daniels Blvd, West Lafayette, IN, USA.
Dementia refers to an umbrella phenotype of many different underlying pathologies with Alzheimer's disease (AD) being the most common type. Neuropathological examination remains the gold standard for accurate AD diagnosis, however, most that we know about AD genetics is based on Genome-Wide Association Studies (GWAS) of clinically defined AD. Such studies have identified multiple AD susceptibility variants with a significant portion of the heritability unexplained and highlighting the phenotypic and genetic heterogeneity of the clinically defined entity.
View Article and Find Full Text PDFComplex genetic interactions affect susceptibility to Alzheimer's disease risk in the BIN1 and MS4A6A loci.
Geroscience
January 2025
Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Erwin Mill Building, 2024 W. Main St, Durham, NC, 27705, USA.
Genetics is the second strongest risk factor for Alzheimer's disease (AD) after age. More than 70 loci have been implicated in AD susceptibility so far, and the genetic architecture of AD entails both additive and nonadditive contributions from these loci. To better understand nonadditive impact of single-nucleotide polymorphisms (SNPs) on AD risk, we examined individual, joint, and interacting (SNPxSNP) effects of 139 and 66 SNPs mapped to the BIN1 and MS4A6A AD-associated loci, respectively.
View Article and Find Full Text PDFIdentification of Alzheimer's disease susceptibility genes by integrating eight human brain single-cell transcriptomes with genome-wide association studies.
J Neurochem
January 2025
Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China.
To date, several studies have integrated genome-wide association studies (GWAS) and expression quantitative trait loci (eQTL) data from bulk tissues to identify novel Alzheimer's disease (AD) genetic variants and susceptibility genes. However, there is highly cell-type-specific nature in different bulk eQTL data. Until now, eQTL data from different brain single cells have been reported.
View Article and Find Full Text PDFsTREM2 Mediates the Correlation Between BIN1 Gene Polymorphism and Tau Pathology in Alzheimer's Disease.
J Alzheimers Dis
September 2024
Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
Article Synopsis
- The study investigates how variations in the BIN1 gene are linked to neuroinflammation and Alzheimer's disease (AD) pathology, focusing on two specific genetic polymorphisms: rs7561528 and rs744373.
- Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Chinese Alzheimer's Biomarker and Lifestyle (CABLE) study, researchers found a significant relationship between BIN1 loci and levels of key Alzheimer's biomarkers in cerebrospinal fluid (CSF), particularly phosphorylated-tau (P-tau), total-tau (T-tau), and microglial activation marker sTREM2.
- The findings suggest that the association between BIN1 loci and tau pathology is
A systems biology-based identification and in vivo functional screening of Alzheimer's disease risk genes reveal modulators of memory function.
Neuron
July 2024
Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, New York, NY, USA; Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA. Electronic address:
Genome-wide association studies (GWASs) have uncovered over 75 genomic loci associated with risk for late-onset Alzheimer's disease (LOAD), but identification of the underlying causal genes remains challenging. Studies of induced pluripotent stem cell (iPSC)-derived neurons from LOAD patients have demonstrated the existence of neuronal cell-intrinsic functional defects. Here, we searched for genetic contributions to neuronal dysfunction in LOAD using an integrative systems approach that incorporated multi-evidence-based gene mapping and network-analysis-based prioritization.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!