A5019627764- Alzheimer's disease research and treatments
- Genetic Associations and Epidemiology
- Bioinformatics and Genomic Networks
- Epigenetics and DNA Methylation
- Dementia and Cognitive Impairment Research
- Nuclear Receptors and Signaling
- Folate and B Vitamins Research
- Mitochondrial Function and Pathology
- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Parkinson's Disease Mechanisms and Treatments
- Diet and metabolism studies
- Machine Learning in Bioinformatics
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Amyotrophic Lateral Sclerosis Research
- MicroRNA in disease regulation
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetic Neurodegenerative Diseases
- Cellular transport and secretion
- Inflammation biomarkers and pathways
- Ginkgo biloba and Cashew Applications
- GDF15 and Related Biomarkers
- Cholinesterase and Neurodegenerative Diseases
- Cholesterol and Lipid Metabolism
- Metabolomics and Mass Spectrometry Studies
University of Washington
2015-2025
VA Puget Sound Health Care System
2012-2024
Geriatric Research Education and Clinical Center
2010-2024
University of Washington Medical Center
2000-2024
University of Puget Sound
2006-2023
University of Kentucky
2023
Alzheimer’s Disease Neuroimaging Initiative
2020
Institute for Neurodegenerative Disorders
2018
The University of Texas Health Science Center at San Antonio
2018
Boston University
2017-2018
The ɛ4 allele of the human apolipoprotein E gene (APOE) is a well-proven genetic risk factor for late onset form Alzheimer's disease (AD). However, biological mechanisms through which contributes to pathophysiology are incompletely understood. three common allel es APOE, ɛ2, ɛ3 and ɛ4, defined by two single nucleotide polymorphisms (SNPs) that reside in coding region exon 4, overlaps with well-defined CpG island (CGI). Both SNPs change not only protein codon but also quantity dinucleotides,...
Abstract As part of a community‐based study Alzheimer's disease (AD) in the African‐American population age 65 and over, we have determined apolipoprotein E (Apo E) genotypes 85 subjects (31 AD patients 54 controls). The €4 allele Apo was strongly associated with this sample. € frequency 40.3% compared 13.9% control group, 22.6% were homozygous for 3.7% ( p = 0.01). This extends association E‐∈4 to nonwhite populations provides further evidence that observed allelic is biologically relevant.
Homozygous or compound heterozygous parkin mutations cause juvenile parkinsonism. Heterozygous are also found in patients with typical Parkinson's disease (PD), but it is unclear whether a single "mutation" patient related to coincidental, because the mutation frequency control subjects unknown. We present comprehensive sequence analysis of subjects.A total 302 and 301 were sequenced, findings replicated 1,260 additional 1,657 subjects.Thirty-four variants detected, which 21 novel; 12...
The apolipoprotein E gene (APOE) is the strongest genetic risk factor for late-onset Alzheimer's disease (AD), yet expression of APOE not clearly understood. For example, it unclear whether AD patients have elevated or decreased why correlation levels RNA and ApoE protein differ across studies. Likewise, has a single CpG island (CGI) that overlaps with its 3'-exon, this CGI's effect unknown. We previously reported CGI highly methylated in human postmortem brain (PMB) methylation altered...
Abstract The apolipoprotein E gene (Apo E) type 4 allele is a genetic risk factor influencing the development and age of onset Alzheimer's disease. Because Parkinson's disease shares many characteristics disease, we studied frequencies Apo genotypes in cohort 52 patients with dementia 61 without dementia. Dementia was determined per National Institute Neurological Communicative Disorders Stroke criteria Mattis Rating Scale (DRS) < 126. Normal cognition defined as DRS > 132. genotype...
Abstract Currently the ε4 allele of apolipoprotein E gene ( APOE ) is strongest genetic risk factor for late onset Alzheimer's disease (AD). However, inheritance not necessary or sufficient development AD. Genetic evidence suggests that multiple loci in a 70 kb region surrounding are associated with AD risk. Even though these could represent surrogate markers linkage disequilibrium allele, they also contribute biological effects independent allele. Our previous study identified SNPs upstream...
Increasing evidence suggests that the Translocase of Outer Mitochondria Membrane 40 (TOMM40) gene may contribute to risk Alzheimer’s disease (AD). Currently, there is no consensus as whether TOMM40 expression up- or down-regulated in AD brains, hindering a clear interpretation TOMM40’s role this disease. The aim study was determine if RNA levels differ between and control brains. We applied RT-qPCR transcription human postmortem brain (PMB) assessed associations these with genetic variants...
This Paper serves a primary purpose of gathering information and conducting research the relevant policies their issues in current stock market China. During process researching analyzing market, major were discovered about China terms policy restrictions investor limitations. The paper identifies four market: 1. Market Volatility Speculation, 2. Lack Corporate Governance Transparency, 3. Regulatory Challenges Inefficiencies, 4. Foreign Investment Barriers Limited Accessibility pathways for...
The Apolipoprotein E (APOE) locus has garnered significant clinical interest because of its association with Alzheimer's disease (AD) and longevity. This genetic appears across multiple genes in the APOE locus. Despite apparent differences between AD longevity, both conditions share a commonality aging-related changes mitochondrial function. is likely due to accumulative biological effects partly exerted by In this study, we investigated structure/function-related markers using oxidative...
Mutations in the p53 tumor-suppressor gene promote increased genomic instability and cancer. WRN gene, encoding a DNA helicase, underlie segmental progeroid Werner syndrome (WS). WS is also associated with elevated cancer risk. The proteins can engage direct protein-protein interactions. We report that excess elicits cellular levels potentiates p53-mediated apoptosis. Importantly, cells derived from patients exhibit an attenuated delayed induction of by UV or topoisomerase I inhibitor...
Abstract Background This study investigates the association between TOMM40 poly‐T length, age at onset, and neuropathology in individuals with Alzheimer's disease (AD) apolipoprotein E ( APOE ) ɛ3/ɛ3 allele. Methods Thirty‐two presenilin 1 PSEN1 mutation carriers AD, 27 2 PSEN2 59 participants late‐onset AD (LOAD), 168 autopsied subjects from a community‐based cohort were genotyped for intron 6 (rs10524523) length using short tandem repeat assays. Results Among mutations, presence of long...
Families with early-onset Alzheimer's disease (AD) sharing a single PSEN2 mutation exhibit wide range of age-at-onset, suggesting that modifier loci segregate within these families. While APOE is known to be an age-at-onset modifier, it does not explain all this variation. We performed genome scan nine such families for influencing while simultaneously controlling variation in the primary (N141I) and APOE. found significant evidence linkage between chromosome 1q23.3 (P < 0.001) when analysis...
Abstract Introduction Inheritance of the ε4 allele apolipoprotein E ( APOE ) increases a person's risk developing both Alzheimer's disease (AD) and Lewy body dementia (LBD), yet underlying mechanisms behind this are incompletely understood. The recent identification reduced DNA methylation in AD postmortem brains prompted study to investigate LBD. Methods Genomic from brain tissues (frontal lobe cerebellum) neuropathological pure (np) controls npAD, LBD + AD, npLBD subjects were bisulfite...
Pathological amyloid-β and α-synuclein are associated with a spectrum of related dementias, ranging from Alzheimer's disease (AD) dementia Lewy bodies (DLB) to Parkinson (PDD). While these diseases share clinical pathological features, they also have unique patterns pathology. However, epigenetic factors that contribute differences remain unknown. In this preliminary study, we explore in DNA methylation transcription five neuropathologically defined groups: cognitively unimpaired controls,...
Abstract Wei and Hemmings [2000: Nat Genet 25:376–377], using 80 British parent–offspring trios, identified a number of NOTCH4 variants haplotypes that showed statistically significant evidence association to schizophrenia. Specifically, the 10 repeat allele (CTG) n marker 8 (TAA) demonstrated excess transmission affected individuals; SNP2 1 SNP2‐(CTG) SNP1 2 ‐SNP2‐(CTG) also associations. In an attempt replicate these findings, we tested for linkage between same five markers used by in 166...
Abstract Alzheimer's disease (AD) is characterized by the presence in brain of amyloid plaques, consisting predominately β peptide (Aβ), and neurofibrillary tangles, primarily tau. Hyper‐phosphorylated‐tau (p‐tau) contributes to neuronal damage, both p‐tau total‐tau (t‐tau) levels are elevated AD cerebrospinal fluid (CSF) compared cognitively normal controls. Our hypothesis was that increased ratios CSF phosphorylated‐tau relative correlate with regulatory region genetic variation kinase or...