A5070892687- Alzheimer's disease research and treatments
- Down syndrome and intellectual disability research
- Dementia and Cognitive Impairment Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Frailty in Older Adults
- Chronic Disease Management Strategies
- Human-Animal Interaction Studies
- Diet and metabolism studies
- Prion Diseases and Protein Misfolding
- Memory and Neural Mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Neurological Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Neurological Disorders and Treatments
- Biochemical effects in animals
- Advanced Neuroimaging Techniques and Applications
- S100 Proteins and Annexins
- Neuroendocrine regulation and behavior
- Olfactory and Sensory Function Studies
- Bioinformatics and Genomic Networks
- Cell death mechanisms and regulation
- Mitochondrial Function and Pathology
- Gut microbiota and health
- Tryptophan and brain disorders
- Genetics and Neurodevelopmental Disorders
University of California, Irvine
2010-2025
University of California System
2005-2024
University of Kentucky
2014-2023
UC Irvine Health
1999-2023
Alzheimer’s Disease Neuroimaging Initiative
2023
University of North Carolina at Chapel Hill
2022
Lady Hardinge Medical College
2022
Czech Academy of Sciences, Institute of Experimental Medicine
2022
Nia Association
2022
ID Genomics (United States)
2022
Soluble oligomers are common to most amyloids and may represent the primary toxic species of amyloids, like Abeta peptide in Alzheimer's disease (AD). Here we show that all soluble tested display a conformation-dependent structure is unique regardless sequence. The vitro toxicity inhibited by oligomer-specific antibody. have distribution human AD brain distinct from fibrillar amyloid. These results indicate different types amyloid suggest they share mechanism toxicity.
Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified genetic sharing 25 disorders from genome-wide association studies 265,218 patients 784,643 control participants assessed relationship to 17 phenotypes 1,191,588 individuals. Psychiatric common variant risk, whereas neurological appear more distinct one another psychiatric disorders. also identified significant between a number...
Amyloid-related degenerative diseases are associated with the accumulation of misfolded proteins as amyloid fibrils in tissue. In Alzheimer disease (AD), accumulates several distinct types insoluble plaque deposits, intracellular Abeta and soluble oligomers relationships between these deposits their pathological significance remains unclear. Conformation dependent antibodies have been reported that specifically recognize assembly states amyloids, including prefibrillar fibrils.We immunized...
Gene expression profiles were assessed in the hippocampus, entorhinal cortex, superior-frontal gyrus, and postcentral gyrus across lifespan of 55 cognitively intact individuals aged 20-99 years. Perspectives on global gene changes that are associated with brain aging emerged, revealing two overarching concepts. First, different regions forebrain exhibited substantially profile age. For example, comparing equally powered groups, 5,029 probe sets significantly altered age compared 1,110...
Accumulation of oxidative damage to mitochondria, protein, and nucleic acid in the brain may lead neuronal cognitive dysfunction. The effects on function, mitochondrial structure, biomarkers were studied after feeding old rats two metabolites, acetyl- l -carnitine (ALCAR) [0.5% or 0.2% (wt/vol) drinking water], and/or R -α-lipoic (LA) [0.2% 0.1% (wt/wt) diet]. Spatial memory was assessed by using Morris water maze; temporal tested peak procedure (a time-discrimination procedure). Dietary...
Abstract Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population society as whole. With numbers of people with ADRDs predicted to rise dramatically across world, scientific community can no longer neglect need for research focusing on among underrepresented ethnoracial diverse groups. The Association International Society Advance Research Treatment (ISTAART; alz.org/ISTAART ) comprises number professional interest areas (PIAs), each major area...
To evaluate the clinical and pathological features of a subgroup patients with Alzheimer disease (AD) who exhibited early disproportionately severe impairments on tests frontal lobe functioning. We hypothesized that these would exhibit greater degree either neurofibrillary tangle (NFT) or senile plaque pathology in lobes than typical AD.We examined neuropsychological profiles NFT accumulation frontal, entorhinal, temporal, parietal cortices 3 AD disproportionate during stages dementia...
Amyloid oligomers are believed to play causal roles in several types of amyloid-related neurodegenerative diseases. Several different amyloid have been reported that differ morphology, size, or toxicity, raising the question pathological significance and structural relationships between oligomers. Annular protofibrils (APFs) described oligomer preparations many amyloidogenic proteins peptides as ring-shaped pore-like structures. They interesting because their morphology is consistent with...
Amyloid beta (Abeta) 1–42 oligomers accumulate in brains of patients with Mild Cognitive Impairment (MCI) and disrupt synaptic plasticity processes that underlie memory formation. Synaptic binding Abeta to several putative receptor proteins is reported inhibit long-term potentiation, affect membrane trafficking induce reversible spine loss neurons, leading impaired cognitive performance ultimately anterograde amnesia the early stages Alzheimer's disease (AD). We have identified a not...
Overexpression of the amyloid precursor protein (APP) gene on chromosome 21 in Down syndrome (DS) has been linked to increased brain levels and early-onset Alzheimer’s disease (AD). An elderly man with phenotypic DS partial trisomy (PT21) lacked triplication APP affording an opportunity study role this pathogenesis dementia. Multidisciplinary studies between ages 66–72 years comprised neuropsychological testing, independent neurological exams, PET imaging 11 C-Pittsburgh compound-B (PiB),...
Microglia are strongly implicated in the development and progression of Alzheimer's disease (AD), yet their impact on pathology lifespan remains unclear. Here we utilize a CSF1R hypomorphic mouse to generate model AD that genetically lacks microglia. The resulting microglial-deficient mice exhibit profound shift from parenchymal amyloid plaques cerebral angiopathy (CAA), which is accompanied by numerous transcriptional changes, greatly increased brain calcification hemorrhages, premature...
Old, middle-aged, and young dogs were compared on discrimination reversal learning acquisition of a delayed-nonmatching-to-sample (DNMS) test recognition memory. DNMS was acquired more rapidly by dogs. Reversal deficits found between aged mixed-breed beagles, but not old beagles. Aged beagles also showed unexpected in reward approach object learning. did show learning, they learned the task slowly than age-matched A detailed analysis response patterns indicated that once present, development...