A5060394127- Alzheimer's disease research and treatments
- Nuclear Receptors and Signaling
- Computational Drug Discovery Methods
- Cholinesterase and Neurodegenerative Diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Cholesterol and Lipid Metabolism
- Neuroscience and Neuropharmacology Research
- Drug Transport and Resistance Mechanisms
- Estrogen and related hormone effects
- Menopause: Health Impacts and Treatments
- Retinoids in leukemia and cellular processes
- Dementia and Cognitive Impairment Research
- Peroxisome Proliferator-Activated Receptors
- Tryptophan and brain disorders
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Cellular transport and secretion
- S100 Proteins and Annexins
- Fatty Acid Research and Health
- Adipose Tissue and Metabolism
- Phytoestrogen effects and research
- Lipid metabolism and disorders
- Stress Responses and Cortisol
- Cancer, Lipids, and Metabolism
- Advanced Glycation End Products research
- Prion Diseases and Protein Misfolding
University of Illinois Chicago
2015-2024
VA Greater Los Angeles Healthcare System
2016
Geriatric Research Education and Clinical Center
2016
University of California, Los Angeles
2016
Indo-American Center
2013
Institute of Cell Biology and Neurobiology
2005-2009
NorthShore University HealthSystem
2000-2006
Northwestern University
2002-2005
University of Chicago
1994-2005
Abbott (United States)
2005
Genetic evidence predicts a causative role for amyloid-β (Aβ) in Alzheimer's disease. Recent debate has focused on whether fibrils (amyloid) or soluble oligomers of Aβ are the active species that contribute to neurodegeneration and dementia. We developed two aggregation protocols consistent production stable oligomeric fibrillar preparations Aβ-(1–42). Here we report inhibit neuronal viability 10-fold more than ∼40-fold unaggregated peptide, with Aβ-(1–42)-induced inhibition significant at...
Extensive research causally links amyloid-β peptide (Aβ) to Alzheimer's disease, although the pathologically relevant Aβ conformation remains unclear. spontaneously aggregates into fibrils that deposit in senile plaques. However, recent <i>in vivo</i> and vitro</i>reports describe a potent biological activity for oligomeric assemblies of Aβ. To consistently prepare vitro</i> fibrillar forms Aβ1–42, detailed knowledge how solution parameters influence structure is required. This manuscript...
Apolipoprotein E (apoE), particularly the e4 allele, is genetically linked to incidence of Alzheimer's disease. ApoE present in extracellular senile plaques and intracellular neurofibrillary tangles associated with In vitro, apoE has been shown bind beta-amyloid (A beta), an amyloidogenic proteolytic product amyloid precursor protein. To analyze interaction A beta apoE, we used Western immunoblotting human beta-(1-40)-peptide incubated conditioned medium from HEK-293 cells transfected either...
Abstract: Little is known about lipid transport and metabolism in the brain. As a further step toward understanding origin function of CNS lipoproteins, we have characterized by size density fractionation lipoprotein particles from human CSF primary cultures rat astrocytes. The fractions were analyzed for esterified free cholesterol, triglyceride, phospholipid, albumin, apolipoproteins (apo) E, AI, AII, J. determined apolipoprotein profiles, gel electrophoresis, electron microscopy, nascent...
The inheritance of the apolipoprotein E (apoE) epsilon4 allele is a prevailing risk factor for sporadic and familial Alzheimer's disease (AD). ApoE isoforms bind directly to amyloid beta (Abeta) peptides both in vitro vivo. Recent studies suggest that association apoE with lipids may modulate its interaction Abeta. We examined binding lipid-associated delipidated apoE3 apoE4 Abeta utilizing solid-phase assay estimated dissociation constants various species. Using native from stably...
The pathological mechanism by which Aβ causes neuronal dysfunction and death remains largely unknown. Deficiencies in fast axonal transport (FAT) were suggested to play a crucial role loss for diverse set of dying back neuropathologies including Alzheimer's disease (AD), but the molecular basis changes FAT undetermined. Recent findings indicate that soluble intracellular oligomeric (oAβ) species may critical AD pathology. Real-time analysis vesicle mobility isolated axoplasms perfused with...
The ε4 allele of apolipoprotein E (apoE) is associated with increased risk for Alzheimer’s disease (AD) and poor outcome after brain injury. In the CNS, apoE expressed by glia, predominantly astrocytes. To define potential biological functions different human isoforms produced within brain, transgenic mice were generated in which apoE3 apoE4 expression under control astrocyte-specific glial fibrillary acidic protein (GFAP) promoter. These animals then bred back to knock-out mice. Human found...
The three human alleles of apolipoprotein E (APOE) differentially influence outcome after CNS injury and affect one's risk developing Alzheimer's disease (AD). It remains unclear how ApoE isoforms contribute to various AD-related pathological changes (e.g., amyloid plaques synaptic neuron loss). Here, we systematically examined whether apoE (E2, E3, E4) exhibit differential effects on dendritic spine density morphology in APOE targeted replacement (TR) mice, which lack AD changes. Using...
Composition of central nervous system lipoproteins affects the metabolism lipoprotein constituents within brain. The epsilon4 allele apolipoprotein E (apoE) is a risk factor for Alzheimer's disease via an unknown mechanism(s). As glia are primary cell type that synthesize apoE, we characterized secreted by astrocytes from wild (WT), apoE (-/-), and transgenic mice expressing human apoE3 or apoE4 in mouse (-/-) background. Nondenaturing size exclusion chromatography demonstrates WT, apoE3,...
Abstract The ϵ4 allele of the Apolipoprotein E (APOE) gene is strongest genetic risk factor for late‐onset Alzheimer's disease (AD), and affects clinical outcomes chronic acute brain damages. mechanisms by which apoE affect diverse diseases disorders may involve modulation glial response to various types damage. We examined activation in a mouse model where each human APOE alleles are expressed under endogenous promoter, as well knock‐out mice. APOE4 mice displayed increased...
To date there is no effective therapy for Alzheimer disease (AD). High levels of circulating high density lipoprotein (HDL) and its main protein, apolipoprotein A-I (apoA-I), reduce the risk cardiovascular disease. Clinical studies show that plasma HDL cholesterol apoA-I are low in patients with AD. investigate if increasing apoA-I/HDL ameliorates AD-like memory deficits amyloid-β (Aβ) deposition, we generated a line triple transgenic (Tg) mice overexpressing mutant forms precursor protein...
Having the apolipoprotein E4 (APOE-ϵ4) allele is strongest genetic risk factor for development of Alzheimer's disease (AD). Accumulation amyloid beta (Aβ) in brain influenced by APOE genotype. Transgenic mice co-expressing five familial AD mutations (5xFAD) presence human alleles (ϵ2, ϵ3 or ϵ4) exhibit genotype-specific differences early Aβ accumulation, suggesting an interaction between and pathology. Whether genotype affects Aβ-plaque-associated neuroinflammation remains unclear. In...
Abstract Background The form(s) of amyloid-β peptide (Aβ) associated with the pathology characteristic Alzheimer's disease (AD) remains unclear. In particular, neurotoxicity intraneuronal Aβ accumulation is an issue considerable controversy; even existence deposits within neurons has recently been challenged by Winton and co-workers. These authors purport that it actually APP being detected antibodies thought to be specific for Aβ. To further address this issue, anti-Aβ antibody was...
Human apolipoprotein E (apoE) isoforms may differentially modulate amyloid-β (Aβ) levels. Evidence suggests physical interactions between apoE and Aβ are partially responsible for these functional effects. However, the apoE/Aβ complex is not a single static structure; rather, it defined by detection methods. Thus, literature results inconsistent difficult to interpret. An ELISA was developed measure soluble in single, quantitative method used address hypothesis that reduced levels of an...