Alzheimer's Disease Sequencing Project Release 4 Whole Genome Sequencing Dataset DOI Creative Commons
Yuk Yee Leung, Wan‐Ping Lee, Amanda B. Kuzma

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 6, 2024

The Alzheimer's Disease Sequencing Project (ADSP) is a national initiative to understand the genetic architecture of and Related Dementias (AD/ADRD) by sequencing whole genomes affected participants age-matched cognitive controls from diverse populations. Genome Center for (GCAD) processed whole-genome data 36,361 ADSP participants, including 35,014 genetically unique which 45% are non-European ancestry, across 17 cohorts in 14 countries this fourth release (R4). This effort identified 387 million bi-allelic variants, 42 short insertions/deletions, 2.2 structural variants. Annotations quality control available all variants samples. Additionally, detailed phenotypes 15,927 10 domains also provided. A linkage disequilibrium panel was created using unrelated AD cases controls. Researchers can access analyze via NIAGADS Data Sharing Service, VariXam tool, or GenomicsDB.

Language: Английский

Mitochondrial Dysfunction in Neurodegenerative Diseases DOI Creative Commons
Han‐Mo Yang

Cells, Journal Year: 2025, Volume and Issue: 14(4), P. 276 - 276

Published: Feb. 13, 2025

Mitochondrial dysfunction represents a pivotal characteristic of numerous neurodegenerative disorders, including Alzheimer's disease, Parkinson's Huntington's and amyotrophic lateral sclerosis. These conditions, distinguished by unique clinical pathological features, exhibit shared pathways leading to neuronal damage, all which are closely associated with mitochondrial dysfunction. The high metabolic requirements neurons make even minor deficiencies highly impactful, driving oxidative stress, energy deficits, aberrant protein processing. Growing evidence from genetic, biochemical, cellular investigations associates impaired electron transport chain activity disrupted quality-control mechanisms, such as mitophagy, the initial phases disease progression. Furthermore, overproduction reactive oxygen species persistent neuroinflammation can establish feedforward cycles that exacerbate deterioration. Recent research has increasingly focused on interventions aimed at enhancing resilience-through antioxidants, small molecules modulate balance fusion fission, or gene-based therapeutic strategies. Concurrently, initiatives identify dependable biomarkers seek detect changes prior manifestation overt symptoms. By integrating current body knowledge, this review emphasizes critical role preserving homeostasis viable approach. It also addresses complexities translating these findings into practice underscores potential innovative strategies designed delay potentially halt processes.

Language: Английский

Citations

1
Mitochondrial DNA copy number and Alzheimer’s disease and Parkinson disease DOI
Pei Qin, Xiaojuan Chen, Panpan Ma

et al.

Mitochondrion, Journal Year: 2025, Volume and Issue: unknown, P. 102032 - 102032

Published: March 1, 2025

Language: Английский

Citations

0
Association between proton pump inhibitors and dementia risk: a Mendelian randomization study DOI Creative Commons

Kexin Xie,

Jing Li,

Chengwei Tang

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 19, 2024

Numerous observational studies suggest associations between proton pump inhibitors (PPIs) and dementia, but causal relationships remain uncertain. Using large-scale genome-wide association study (GWAS) data, we performed univariable Mendelian randomization (UVMR) analysis to assess the causality five PPI types, all-cause dementia its subtypes. Confounders were controlled through multivariable MR (MVMR) isolate PPIs' direct effects on dementia. Heterogeneity pleiotropy assessments, leave-one-out analysis, conducted validate robustness of our results. Initial UVMR estimates suggested that lansoprazole (odds ratio [OR] 1.291; 95%confidence interval [CI] 1.001–1.665; p = 0.049) pantoprazole (OR 1.118; 95% CI 1.014–1.233; 0.025) potentially increased VD risk, with their respective also discovered in MVMR. Additionally, FTD was found reversely increase rabeprazole use 1.086; 1.011–1.167; 0.023). However, after adjustment for false discovery rate (FDR), none these remained statistically significant (pFDR> 0.05). The results is supported by consistent across complementary methods absence pleiotropy. Our indicates no robust risk. Thus, it inappropriate restrict clinically justified prescriptions merely due potential cognitive risks.

Language: Английский

Citations

3
Alzheimer's Disease Sequencing Project Release 4 Whole Genome Sequencing Dataset DOI Creative Commons
Yuk Yee Leung, Wan‐Ping Lee, Amanda B. Kuzma

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 6, 2024

The Alzheimer's Disease Sequencing Project (ADSP) is a national initiative to understand the genetic architecture of and Related Dementias (AD/ADRD) by sequencing whole genomes affected participants age-matched cognitive controls from diverse populations. Genome Center for (GCAD) processed whole-genome data 36,361 ADSP participants, including 35,014 genetically unique which 45% are non-European ancestry, across 17 cohorts in 14 countries this fourth release (R4). This effort identified 387 million bi-allelic variants, 42 short insertions/deletions, 2.2 structural variants. Annotations quality control available all variants samples. Additionally, detailed phenotypes 15,927 10 domains also provided. A linkage disequilibrium panel was created using unrelated AD cases controls. Researchers can access analyze via NIAGADS Data Sharing Service, VariXam tool, or GenomicsDB.

Language: Английский

Citations

1