Gerard D. Schellenberg
A5091305213- Alzheimer's disease research and treatments
- Genetic Associations and Epidemiology
- Bioinformatics and Genomic Networks
- Genomics and Rare Diseases
- Dementia and Cognitive Impairment Research
- Parkinson's Disease Mechanisms and Treatments
- Nutrition, Genetics, and Disease
- Genetics and Neurodevelopmental Disorders
- Genomic variations and chromosomal abnormalities
- Epigenetics and DNA Methylation
- Folate and B Vitamins Research
- Nuclear Receptors and Signaling
- Health, Environment, Cognitive Aging
- Neurological diseases and metabolism
- Biological Research and Disease Studies
- Autism Spectrum Disorder Research
- RNA regulation and disease
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Prion Diseases and Protein Misfolding
- Amyotrophic Lateral Sclerosis Research
- Cholinesterase and Neurodegenerative Diseases
- RNA Research and Splicing
- DNA Repair Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Genomics and Phylogenetic Studies
University of Pennsylvania
2016-2025
Dr. John T. Macdonald Foundation
2016-2024
Institute on Aging
2010-2024
California University of Pennsylvania
2012-2024
Boston University
2016-2024
Case Western Reserve University
2016-2024
Penn Center for AIDS Research
2022-2024
Genomics (United Kingdom)
2022
University of Miami
2017
University of Washington
2003-2017
A candidate gene for the chromosome 1 Alzheimer's disease (AD) locus was identified (STM2). The predicted amino acid sequence STM2 is homologous to that of recently cloned 14 AD (S182). point mutation in STM2, resulting substitution an isoleucine asparagine (N141l), affected people from Volga German kindreds. This N141l occurs at residue conserved human S182 and mouse homolog. presence missense mutations subjects two highly similar genes strongly supports hypothesis both are pathogenic.
Werner's syndrome (WS) is an inherited disease with clinical symptoms resembling premature aging. Early susceptibility to a number of major age-related diseases key feature this disorder. The gene responsible for WS (known as WRN ) was identified by positional cloning. predicted protein 1432 amino acids in length and shows significant similarity DNA helicases. Four mutations patients were identified. Two the are splice-junction mutations, result being exclusion exons from final messenger...
Several lines of evidence point to genetic involvement in autism spectrum disorders (ASDs), neurodevelopmental and neuropsychiatric characterized by impaired verbal communication social interaction. The clinical complexities the condition make it difficult identify susceptibility factors, but two related studies now present robust for a involvement. first, genome-wide association study, identifies six single-nucleotide polymorphisms strongly associated with autism. These variants lie between...
Abstract Frontotemporal dementia with parkinsonism, chromosome 17 type (FTDP‐17), a recently defined disease entity, is clinically characterized by personality changes sometimes associated psychosis, hyperorality, and diminished speech output, disturbed executive function nonfluent aphasia, rigidity. Neuropathological include frontotemporal atrophy often of the basal ganglia, substantia nigra, amygdala. Neurofibrillary tangles (NFTs) are seen in some but not all families. Inheritance...
Linkage analysis was used to search the genome for chromosomal regions harboring familial Alzheimer's disease genes. Markers on chromosome 14 gave highly significant positive lod scores in early-onset non-Volga German kindreds; a Zmax of 9.15 (theta = 0.01) obtained with marker D14S43 at 14q24.3. One family yielded score 4.89 0.0). When no assumptions were made about age-dependent penetrance, results still (Zmax 5.94, theta 0.0), despite loss power detect linkage under these conditions....
<h3>Context</h3> Age-specific incidence rates for dementia and Alzheimer disease (AD) are important research clinical practice. Incidence estimates the United States few vary with population sampled study design; we present data that will contribute to a consensus of these rates. <h3>Objectives</h3> To provide age-specific AD estimate association sex, educational level, apolipoprotein E genotype onset. <h3>Design</h3> Prospective cohort study; begun in 1994 follow-up interviews every 2...
Patients with Alzheimer9s disease (AD) have elevations of fasting plasma insulin that are hypothesized to be associated disrupted brain metabolism. We examined paired fasted and CSF levels in 25 patients AD 14 healthy age-matched adults determined whether were related severity dementia apolipoprotein E-ϵ4 homozygosity, a known genetic risk factor for AD. The had lower insulin, higher reduced CSF-to-plasma ratio when compared adults. differences greater more advanced who not homozygotes...
<h3>Importance</h3> Although vitamin E and memantine have been shown to beneficial effects in moderately severe Alzheimer disease (AD), evidence is limited mild moderate AD. <h3>Objective</h3> To determine if (alpha tocopherol), memantine, or both slow progression of AD patients taking an acetylcholinesterase inhibitor. <h3>Design, Setting, Participants</h3> Double-blind, placebo-controlled, parallel-group, randomized clinical trial involving 613 with initiated August 2007 concluded...
Frontotemporal dementia with parkinsonism, chromosome 17 type (FTDP-17) is caused by mutations in the tau gene, and signature lesions of FTDP-17 are filamentous inclusions. Tau may be pathogenic either altering protein function or gene regulation. Here we show that missense, silent, intronic can increase decrease splicing exon 10 (E10) acting on 3 different cis-acting regulatory elements. These elements include an enhancer strengthened (mutation N 279 K ) destroyed Δ280 ), resulting...
Pallido-ponto-nigral degeneration (PPND) is one of the most well characterized familial neurodegenerative disorders linked to chromosome 17q21–22. These hereditary are known collectively as frontotemporal dementia (FTD) and parkinsonism 17 (FTDP-17). Although clinical features associated regional variations in neuronal loss observed different FTDP-17 kindreds diverse, diagnostic lesions brains tau-rich filaments cytoplasm specific subpopulations neurons glial cells. The microtubule protein...
The genetics underlying the autism spectrum disorders (ASDs) is complex and remains poorly understood. Previous work has demonstrated an important role for structural variation in a subset of cases, but lacked resolution necessary to move beyond detection large regions potential interest identification individual genes. To pinpoint genes likely contribute ASD etiology, we performed high density genotyping 912 multiplex families from Autism Genetics Resource Exchange (AGRE) collection...
Objectives: To determine whether genotypes at CLU, PICALM, and CR1 confer risk for Alzheimer disease (AD) AD associated with these genes is influenced by apolipoprotein E (APOE) genotypes.
<b>Objective</b> The joint effects of total cholesterol (TC) levels and the APOE genotype in Alzheimer9s disease (AD) were evaluated because previous reports that locus ϵ4 allele was associated with both late-onset AD elevated TC. <b>Design</b> Logistic regression used to determine genotype, TC, age, sex on prediction a community-based study 206 cases 276 controls. <b>Results</b> relationship dependent sex. However, current TC level does not fully explain ϵ4-Alzheimer9s association. Affected...
Background Identifying individuals at risk for developing Alzheimer disease (AD) is of utmost importance. Although genetic studies have identified AD-associated SNPs in APOE and other genes, information has not been integrated into an epidemiological framework prediction. Methods findings Using genotype data from 17,008 AD cases 37,154 controls the International Genomics Alzheimer's Project (IGAP Stage 1), we (at p < 10−5). We then these a Cox proportional hazard model using subset 6,409...
Each additional copy of the apolipoprotein E4 (APOE4) allele is associated with a higher risk Alzheimer's dementia, while APOE2 lower it not yet known whether homozygotes have particularly low risk. We generated dementia odds ratios and other findings in more than 5,000 clinically characterized neuropathologically cases controls. APOE2/2 was compared to APOE2/3 3/3, an exceptionally ratio APOE4/4, impact APOE4 gene dose significantly greater confirmed group 24,000 unconfirmed Finding...
<h3>Objective</h3>To test for an association between the apolipoprotein E (APOE) ϵ4 allele and dementias with synucleinopathy.<h3>Design</h3>Genetic case-control study.<h3>Setting</h3>Academic research.<h3>Patients</h3>Autopsied subjects were classified into 5 categories: dementia high-level Alzheimer disease (AD) neuropathologic changes (NCs) but without Lewy body (LBD) NCs (AD group; n = 244), LBDNCs ADNCs (LBD-AD 224), no or low levels of (pure DLB [pDLB] 91), Parkinson (PDD) (n 81),...