A5012334998- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Parkinson's Disease Mechanisms and Treatments
- Prion Diseases and Protein Misfolding
- Amyotrophic Lateral Sclerosis Research
- Neurological diseases and metabolism
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Genomics and Rare Diseases
- Folate and B Vitamins Research
- Nuclear Receptors and Signaling
- Genetics and Neurodevelopmental Disorders
- Genetic Associations and Epidemiology
- Cholinesterase and Neurodegenerative Diseases
- Lipoproteins and Cardiovascular Health
- Cellular transport and secretion
- Genomic variations and chromosomal abnormalities
- Trace Elements in Health
- Cholesterol and Lipid Metabolism
- Bioinformatics and Genomic Networks
- GDF15 and Related Biomarkers
- Genetic Neurodegenerative Diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Selenium in Biological Systems
- Congenital heart defects research
- Protein Kinase Regulation and GTPase Signaling
Indiana University – Purdue University Indianapolis
2012-2025
Indiana University School of Medicine
2012-2025
Children's Hospital of Philadelphia
2018-2024
Hospital of the University of Pennsylvania
2024
University of Pennsylvania
2019-2023
Genomics (United Kingdom)
2019-2021
Institute for Transfusion Medicine
2019
Boston University
2017-2018
Framingham Heart Study
2018
Institute for Neurodegenerative Disorders
2018
Familial multiple system tauopathy with presenile dementia (MSTD) is a neurodegenerative disease an abundant filamentous tau protein pathology. It belongs to the group of familial frontotemporal dementias Parkinsonism linked chromosome 17 (FTDP-17), major class inherited dementing disorders whose genetic basis unknown. We now report G A transition in intron following exon 10 gene for microtubule-associated MSTD. The mutation located at 3' neighboring nucleotide GT splice-donor site and...
Alzheimer's disease is a form of localized amyloidosis characterized by cerebral cortical amyloid plaques, neurofibrillary tangles, and deposits within the walls leptomeningeal vessels. Although most cases are sporadic, kindreds with autosomal-dominant inheritance syndrome suggest that single mutation may be important in pathogenesis. Direct sequencing DNA from family autopsy-proven revealed amino acid substitution (Phe for Val) transmembrane domain precursor protein. This correlates...
The tau gene has been found to be the locus of dementia with rigidity linked chromosome 17. Exonic and intronic mutations have described in a number families. Here we describe P301S mutation exon 10 new family. Two members this family were affected. One individual presented frontotemporal dementia, whereas his son corticobasal degeneration, demonstrating that same primary defect can lead 2 distinct clinical phenotypes. Both individuals developed rapidly progressive disease third decade....
Background.Studies concerning the effect of different types leisure activities on various cognitive domains are limited.This study tests hypothesis that mental, physical, and social have a domain-specific protection against decline. Methods.A cohort geographically defined population in China was examined 2003-2005 followed for an average 2.4 years.Leisure were assessed 1,463 adults aged 65 years older without or physical impairment at baseline, their performances tested baseline follow-up...
STAT6 (signal transducer and activator of transcription 6) is a factor that plays central role in the pathophysiology allergic inflammation. We have identified 16 patients from 10 families spanning three continents with profound phenotype early-life onset immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, anaphylaxis. The cases were either sporadic (seven...
Neurofibrillary lesions made of hyperphosphorylated microtubule-associated protein tau constitute not only one the defining neuropathological features Alzheimer disease but also are present in a number other neurodegenerative diseases with dementia. Here we describe novel autosomal dominant named familial "multiple system tauopathy presenile dementia," which is characterized by abundant fibrillary deposits both neurons and glial cells. There no detectable beta-amyloid. The form twisted...
The Alzheimer's disease (AD)-associated presenilin (PS) proteins are required for the γ-secretase cleavages of β-amyloid precursor protein and site 3 (S3) protease cleavage Notch. These intramembrane release amyloid-β peptide (Aβ), including pathogenic 42-aa variant (Aβ 42 ), as well Notch intracellular domains (AICD, NICD). Whereas Aβ is generated by endoproteolysis in middle transmembrane domain, AICD NICD at analogous positions close to cytoplasmic border domain. Numerous mutations...
Abstract As part of an ongoing investigation into the organization and regulation flavonoid biosynthetic pathway, two Arabidopsis thaliana expressed sequence tag (EST) clones (153O10T7 YAY780) with high homology to leucoanthocyanidin dioxygenase (LDOX) or flavonol synthase (FLS) were identified. EST YAY780 was sequenced found encode a protein 49 78% identical all LDOX sequences in database. 153O10T7 used isolate genomic clone encoding 59 61% identity petunia (Petunia hybrida) potato (Solanum...
Coding region and intronic mutations in the tau gene cause frontotemporal dementia parkinsonism linked to chromosome 17. Intronic some missense increase splicing of exon 10, leading an increased ratio four-repeat three-repeat isoforms. Secondary structure predictions have led proposal that one mutation destabilize a putative RNA stem-loop located close splice-donor site intron after 10. We determined three-dimensional this 10 regulatory element by NMR spectroscopy. show it forms stable,...
Exonic and intronic mutations in Tau cause familial neurodegenerative syndromes characterized by frontotemporal dementia dysfunction of multiple cortical subcortical circuits. Here we describe a G389R mutation exon 13 Tau. When 38 years old, the proband presented with progressive aphasia memory disturbance, followed apathy, indifference, hyperphagia. Repeated magnetic resonance imaging showed dramatic progression cerebral atrophy. Positron emission tomography revealed marked glucose...
TDP-43 has been identified as the pathological protein in majority of cases frontotemporal lobar degeneration and amyotrophic lateral sclerosis (ALS). TARDBP mutations have so far uniquely associated with familial sporadic ALS. We describe clinicopathological genetic findings a carrier novel K263E variation, who developed dementia, supranuclear palsy, chorea, but no signs motor neuron disease. Neuropathologic examination revealed neuronal glial TDP-43-immunoreactive deposits, predominantly...
Selenium is a trace element associated with antioxidant activity and considered to be protective agent against free radicals through enhanced enzyme activity. Studies on selenium cognitive function or Alzheimer's disease have yielded inconsistent results. A cross-sectional survey of 2,000 rural Chinese aged 65 years older from two provinces in the People's Republic China was conducted December 2003 May 2005 by use Community Screening Instrument for Dementia, Consortium Establish Registry...
<b>Background:</b> Anticholinergic properties of certain medications often go unrecognized, and are frequently used by the elderly population. Few studies have yet defined long-term impact these on incidence cognitive impairment. <b>Methods:</b> We report a 6-year longitudinal, observational study, evaluating 1,652 community-dwelling African American subjects over age 70 years who were enrolled in Indianapolis-Ibadan Dementia Project between 2001 2007 had normal function at baseline. The...
TREM2 encodes for triggering receptor expressed on myeloid cells 2 and has rare, coding variants that associate with risk late-onset Alzheimer's disease (LOAD) in Caucasians of European North-American origin. This study evaluated the role LOAD African-American (AA) subjects. We performed exonic sequencing validation two independent cohorts >800 selected six (p.R47H, p.R62H, p.D87N, p.E151K, p.W191X, p.L211P) case-control analyses a total 906 cases vs. 2,487 controls.We identified significant...
To assess the relative frequency of unique mutations and their associated characteristics in 97 individuals with progranulin (GRN), an important cause frontotemporal lobar degeneration (FTLD).A 46-site International Frontotemporal Lobar Degeneration Collaboration was formed to collect cases FTLD TAR DNA-binding protein 43-kDa (TDP-43)-positive inclusions (FTLD-TDP). We identified FTLD-TDP pathogenic GRN (GRN+ FTLD-TDP), assessed genetic clinical characteristics, compared them 453 patients...
Pathological aggregates of phosphorylated TDP-43 characterize amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP), two devastating groups neurodegenerative disease. Kinase hyperactivity may be a consistent feature ALS FTLD-TDP, as is not observed in the absence neurodegeneration. By examining changes phosphorylation state, we have identified kinases controlling C. elegans model ALS. In this kinome-wide survey, homologs tau tubulin 1 2 (TTBK1 TTBK2), which...
ABSTRACT Background: There is little information on the association of APOEe4 allele and AD risk in African populations. In previous analyses from Indianapolis-Ibadan dementia project, we have reported that APOE ε4 increased for Alzheimer's disease (AD) Americans but not Yoruba. This study represents a replication this earlier work using enriched cohorts extending analysis to include cognitive decline. Methods: longitudinal two community dwelling elderly Yoruba Americans, genotyping was...
Frontotemporal dementia (FTD) and Alzheimer's disease are the most common forms of early-onset dementia. Dominantly inherited mutations in
Frontotemporal dementia (FTD) and Alzheimer's disease (AD) are the most common forms of early-onset dementia. Unlike AD, FTD begins with behavioral changes before development cognitive impairment. Dominantly inherited mutations in MAPT, microtubule-associated protein tau gene, give rise to cases parkinsonism linked chromosome 17. These individuals develop abundant filamentous inclusions brain cells absence β-amyloid deposits. Here, we used cryo-electron microscopy determine structures...