A5091130759- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Genetic Associations and Epidemiology
- Genomics and Rare Diseases
- Health, Environment, Cognitive Aging
- Bioinformatics and Genomic Networks
- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Metabolomics and Mass Spectrometry Studies
- Biological Research and Disease Studies
- Ethics in Clinical Research
- Nutrition, Genetics, and Disease
- S100 Proteins and Annexins
- Diet and metabolism studies
- Nutritional Studies and Diet
- Genomic variations and chromosomal abnormalities
- GDF15 and Related Biomarkers
- Folate and B Vitamins Research
- Mitochondrial Function and Pathology
- MicroRNA in disease regulation
- RNA modifications and cancer
- Amyotrophic Lateral Sclerosis Research
- Genetic and phenotypic traits in livestock
- RNA Research and Splicing
- Blood Pressure and Hypertension Studies
Columbia University
2016-2025
NewYork–Presbyterian Hospital
2015-2025
Columbia University Irving Medical Center
2015-2024
New York Hospital Queens
2015-2024
Mayo Clinic in Florida
2024
Royal College of Physicians
2024
Pontificia Universidad Católica Madre y Maestra
2017-2023
College of Physicians of Philadelphia
2023
Nia Association
2022
ID Genomics (United States)
2022
Abstract Introduction Blood‐based Alzheimer's disease (AD) biomarkers provide opportunities for community studies and across ethnic groups. We investigated blood biomarker concentrations in the Washington Heights‐Inwood Columbia Aging Project (WHICAP), a multi‐ethnic study of aging dementia. Methods measured plasma amyloid beta (Aβ)40, Aβ42, total tau (t‐tau), phosphorylated (p‐tau)181, p‐tau217, neurofilament light chain (NfL) 113 autopsied participants (29% with high AD neuropathological...
Common single nucleotide polymorphisms in the SORL1 gene have been associated with late onset Alzheimer disease (LOAD), but causal variants not fully characterized nor has mechanism established. The study was undertaken to identify functional mutations patients LOAD.
To detect rare coding variants underlying loci detected by genome-wide association studies (GWAS) of late onset Alzheimer disease (LOAD).We conducted targeted sequencing ABCA7, BIN1, CD2AP, CLU, CR1, EPHA1, MS4A4A/MS4A6A, and PICALM in 3 independent LOAD cohorts: 176 patients from 124 Caribbean Hispanics families, 120 33 unaffected individuals the 129 National Institute on Aging Family Study; 263 unrelated Canadian European ancestry (210 sporadic 53 controls). Rare found at least 2 data sets...
The risk of developing Alzheimer's disease (AD) significantly increases in individuals carrying the APOEε4 allele. Elderly cognitively healthy with also exist, suggesting presence cellular mechanisms that counteract pathological effects APOEε4; however, these are unknown. We hypothesized carriers without dementia might carry genetic variations could protect them from APOEε4-mediated AD pathology. To test this, we leveraged whole-genome sequencing (WGS) data National Institute on Aging...
Abstract BACKGROUND Alzheimer's disease (AD) biomarkers can help differentiate cognitively unimpaired (CU) individuals from mild cognitive impairment (MCI) and dementia. The role of AD in predicting needs examination. METHODS In 628 CU a multi‐ethnic cohort, amyloid beta (Aβ)42, Aβ40, phosphorylated tau‐181 (p‐tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL) were measured plasma. RESULTS Higher baseline levels p‐tau181/Aβ42 ratio associated with an increased...
Abstract INTRODUCTION Clinical research in Alzheimer's disease (AD) lacks cohort diversity despite being a global health crisis. The Asian Cohort for Disease (ACAD) was formed to address underrepresentation of Asians research, and limited understanding how genetics non‐genetic/lifestyle factors impact this multi‐ethnic population. METHODS ACAD started fully recruiting October 2021 with one central coordination site, eight recruitment sites, two analysis sites. We developed comprehensive...
Blood-based Alzheimer's disease (AD) biomarkers have been increasingly employed for diagnostic, prognostic, and therapeutic monitoring purposes, due to accuracy in distinguishing AD pathophysiologic process. Compared other p-tau isoforms, plasma p-tau217 exhibits stronger associations with hallmarks CSF brain. However, most studies conducted non-Hispanic Whites, limiting our understanding of the performances utility these across ethnicities. We examined a cohort Peruvians from GAPP study,...
Alzheimer's disease (AD) has been associated with cardiovascular and cerebrovascular risk factors (CVRFs) during middle age later is frequently accompanied by pathology at death. An interaction between CVRFs genetic variants might explain the pathogenesis. Genome-wide, gene CVRF analyses for AD, in 6568 patients 8101 controls identified FMNL2 (p = 6.6 × 10
Importance Cerebrospinal fluid (CSF) and plasma biomarkers can detect biological evidence of Alzheimer disease (AD), but their use in low-resource environments among minority ethnic groups is limited. Objective To assess validated for AD adults Caribbean Hispanic ethnicity. Design, Setting, Participants In this decision analytical modeling study, were recruited between January 1, 2018, April 30, 2022, underwent detailed clinical assessments venipuncture. A subsample participants also...
In the context of late-onset Alzheimer's disease (LOAD) over 20 genes have been identified but, aside APOE, all show small effect sizes, leaving a large part genetic component unexplained. Admixed populations, such as Caribbean Hispanics, can provide valuable contribution because their unique profile and higher incidence disease. We aimed to identify novel loci associated with LOAD.About 4514 unrelated Hispanics (2451 cases 2063 controls) were selected for genome-wide association analysis....
The present study identified potential genetic modifiers that may delay or accelerate age at onset of familial Alzheimer disease (AD) by examining in PSEN1 mutation carrier families, and further investigation these provide insight into the pathobiology AD therapeutic measures.To identify variants modify AD.Using a subset Caribbean Hispanic families carry p.G206A mutation, we performed 2-stage genome study. from an ongoing served as discovery set, cohort those with LOAD confirmation set. To...
To identify rare causal variants underlying known loci that segregate with late-onset Alzheimer's disease (LOAD) in multiplex families.We analyzed whole genome sequences (WGS) from 351 members of 67 Caribbean Hispanic (CH) families Dominican Republic and New York multiply affected by LOAD. Members CH additional 47 Caucasian underwent WGS as a part the Disease Sequencing Project (ADSP). All families, an 48 independent case-control cohort were subsequently genotyped for validation. Patients...
Inflammation plays a major role in cognitive aging. Most studies on peripheral inflammation and aging focused selected inflammatory biomarkers. However, markers are regulated influenced by each other, it is therefore important to consider more comprehensive panel of better capture diverse immune pathways characterize the overall profile individuals. We explored 23 circulating biomarkers using data from 1,743 participants without dementia (≥ 65 years-old) community-based, multiethnic...
Pantothenate kinase-associated neurodegeneration (PKAN) is a rare, autosomal recessive neurological disorder characterized by the progressive degeneration of specific regions in brain and invariably fatal. Several individuals families affected PKAN were known to live an isolated region southwestern province Dominican Republic had been previously studied. Forty-six with 34 evaluated for disease manifestations using PKAN-Disease Rating Scale Leiter-3 Cognitive Neuropsychological assessment. We...
We investigated genetic regulators of circulating plasma metabolites to identify pathways underlying biochemical changes in clinical and biomarker-assisted diagnosis Alzheimer's disease (AD). computed metabolite quantitative trait loci by using whole genome sequencing small molecule from 229 older adults with AD 322 age-matched healthy controls. Unbiased associations between 6,881 332,772 common variants were tested, adjusted for age, sex, both metabolomic genomic principal components....
In a whole-exome sequencing study of multiplex Alzheimer's disease (AD) families, we investigated three neuronal ceroid lipofuscinosis genes that have been linked to retromer, an intracellular trafficking pathway associated with AD: 3 (CLN3), 5 (CLN5), and cathepsin D (CTSD). We identified missense variant in CLN5 c.A959G (p.Asn320Ser) segregated AD. find this causes glycosylation defects the expressed protein, which it be retained endoplasmic reticulum reduced delivery endolysosomal...
Abstract Blood‐based phosphorylated tau (Ptau) 181 and 217 biomarkers are sensitive specific for Alzheimer's disease. In this racial/ethnically diverse cohort study, participants were classified as biomarker positive (Ptau+) or negative (Ptau‐) based on Ptau concentrations cognitively impaired (Sym) unimpaired (Asym). The four groups, Ptau‐/Asym, Ptau+/Asym, Ptau‐/Sym, Ptau+/Sym, differed by age, APOE‐4 allele frequency, total tau, neurofilament light chain, cortical thickness measured MRI....
The National Institute on Aging Late-Onset Alzheimer's Disease Family Based Study (NIA-LOAD FBS) was established to study the genetic etiology of disease (AD).
The heterogeneity of the whole-exome sequencing (WES) data generation methods present a challenge to joint analysis. Here we bioinformatics strategy for joint-calling 20,504 WES samples collected across nine studies and sequenced using ten capture kits in fourteen centers Alzheimer's Disease Sequencing Project. joint-genotype called variant-called format (VCF) file contains only positions within union kits. VCF was then processed specifically account batch effects arising from use different...
Imputation has become a standard approach in genome-wide association studies (GWAS) to infer silico untyped markers. Although feasibility for common variants imputation is well established, we aimed assess rare and ultra-rare variants' an admixed Caribbean Hispanic population (CH).We evaluated accuracy CH (N = 1,000), focusing on (0.1% ≤ minor allele frequency (MAF) 1%) (MAF < 0.1%) variants. We used two reference panels, the Haplotype Reference Consortium (HRC; N 27,165) 1000 Genome Project...
Polygenic risk scores (PRSs) assess the individual genetic propensity to a condition by combining sparse information scattered across loci, often displaying small effect sizes. Most PRSs are constructed in European-ancestry populations, limiting their use other ethnicities. Here we and validated PRS for late-onset Alzheimer's Disease (LOAD) Caribbean Hispanics (CH).