A5076939097- Dementia and Cognitive Impairment Research
- Alzheimer's disease research and treatments
- Parkinson's Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Neurobiology of Language and Bilingualism
- Neurological Disease Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Receptor Mechanisms and Signaling
- Cerebrovascular and Carotid Artery Diseases
- Memory and Neural Mechanisms
- Advanced Neuroimaging Techniques and Applications
- Neurotransmitter Receptor Influence on Behavior
- Tryptophan and brain disorders
- Spatial Neglect and Hemispheric Dysfunction
- Stochastic processes and financial applications
- Risk and Portfolio Optimization
- Functional Brain Connectivity Studies
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Stress Responses and Cortisol
- Cardiovascular Health and Disease Prevention
- Health, Environment, Cognitive Aging
- Neurological disorders and treatments
- Ginkgo biloba and Cashew Applications
- Genetic Associations and Epidemiology
- Capital Investment and Risk Analysis
University of California, San Diego
2018-2025
Mass General Brigham
2025
Harvard University
2025
Brigham and Women's Hospital
2025
Massachusetts General Hospital
2025
VA San Diego Healthcare System
2021
University of Washington
2013-2020
Harborview Medical Center
2015-2020
Chelyabinsk State Medical Academy
2004
Plasma biomarkers related to amyloid, tau, and neurodegeneration (ATN) show great promise for identifying these pathological features of Alzheimer's Disease (AD) as shown by recent clinical studies selected autopsy studies. We have evaluated ATN plasma in a series 312 well-characterized longitudinally followed research subjects with available within 5 years or less before examined relation spectrum AD pathologies. Aβ42, Aβ40, total Tau, P-tau181, P-tau231 neurofilament light (NfL) were...
Blood-based biomarkers for amyloid beta and phosphorylated tau show good diagnostic accuracies agreements with their corresponding CSF neuroimaging in the amyloid/tau/neurodegeneration [A/T/(N)] framework Alzheimer's disease. However, blood-based neurodegeneration marker neurofilament light is not specific to disease while total-tau shows lack of correlation total-tau. Recent studies suggest that blood originates principally from peripheral, non-brain sources. We sought address this...
Abstract Blood phosphorylated tau (p-tau) biomarkers, including p-tau217, show high associations with Alzheimer’s disease (AD) neuropathologic change and clinical stage. Certain plasma p-tau217 assays recognize forms additionally at threonine-212, but the contribution of p-tau212 alone to AD is unknown. We developed a blood-based immunoassay that specific without cross-reactivity p-tau217. Here, we examined diagnostic utility p-tau212. In five cohorts ( n = 388 participants), showed...
Patients with Alzheimer's disease (AD) little or no quantifiable insoluble brain tau neurofibrillary tangle (NFT) pathology demonstrate stronger clinical benefits of therapies than those advanced NFTs. The formation NFTs can be prevented by targeting the intermediate soluble assemblies (STAs). However, biochemical understanding and biomarkers STAs are lacking. We show that Tris-buffered saline-soluble aggregates from autopsy-verified AD tissues include core sequence ~tau258-368. In...
Objective The purpose of this study was to determine the sensitivity and specificity α‐synuclein seed amplification assay (αSyn‐SAA) in antemortem postmortem cerebrospinal fluid (CSF) autopsy‐confirmed patients with different distributions pathological αSyn, co‐pathologies, clinical diagnoses. Methods αSyn‐SAA used test CSF samples from 119 subjects a variety syndromes standardized neuropathological examinations Oregon Health Science University (OHSU) California San Diego (UCSD; 56...
Tau neurofibrillary tangles (NFTs) in the presence of amyloid-β (Aβ) plaques are required for diagnosis Alzheimer's Disease (AD) and closely track with cognitive impairment, yet cognitively normal aged individuals frequently exhibit NFTs arising from tau seed accumulation. This may suggest that not all species equally pathogenic raises question whether unidentified modifications augment seeding activity neurodegeneration AD. We investigated how biochemical relate to clinicopathological...
The ability to map the functional connectivity of discrete cell types in intact mammalian brain during behavior is crucial for advancing our understanding function normal and disease states. We combined designer receptor exclusively activated by drug (DREADD) technology behavioral imaging with μPET [18F]fluorodeoxyglucose (FDG) generate whole-brain metabolic maps cell-specific circuits awake, freely moving state. have termed this approach DREADD-assisted mapping (DREAMM) documented its rats...
To examine whether domain-specific patterns of cognitive impairment and trajectories decline differed in patients with clinically diagnosed Parkinson disease dementia (PDD) (N = 29) autopsy-confirmed Lewy bodies (DLB) 58) or Alzheimer (AD) 174) to determine the impact pooling PDD DLB clinical trials targeting cognition.
Given prior work demonstrating that mild cognitive impairment (MCI) can be empirically differentiated into meaningful subtypes, we applied actuarial methods to comprehensive neuropsychological data from the University of California San Diego Alzheimer's Disease Research Center (ADRC) in order identify subgroups within ADRC participants without dementia and examine cognitive, biomarker, neuropathologic trajectories.Cluster analysis was performed on baseline (n = 738; mean age 71.8). Survival...
Primary age-related tauopathy (PART) refers to tau neurofibrillary tangles restricted largely the medial temporal lobe in absence of significant beta-amyloid plaques. PART has been associated with cognitive impairment, but contributions from concomitant limbic TDP-43 encephalopathy neuropathologic change (LATE-NC) are underappreciated.
Tau deposition within neurons marks Alzheimer's disease (AD) neuropathology, suggesting that tau may contribute to cellular dysfunction and death. In AD, somatic mutations accumulate in neurons, with features suggest deleterious effects on function. To examine the relationship between mutation, we isolated according pathology performed single-cell whole-genome sequencing tau+, tau-, tau-agnostic from 13 individuals as well 15 control individuals. We found AD regardless of status, exhibited...
Patients with earlier age at onset of sporadic Alzheimer disease (AD) are more likely than those later to present atypical clinical and cognitive features. We sought determine whether this age-related heterogeneity is mediated by different topographic distributions tau-aggregate neurofibrillary tangles (NFTs) or variable amounts concomitant non-AD neuropathology.
To characterize age-related clinical heterogeneity in Alzheimer disease (AD) and determine whether it is modified by APOE genotype or concomitant non-AD pathology, we analyzed data from 1,750 patients with sporadic, pathologically confirmed severe AD.In this retrospective cohort study, regression mixed effects models assessed of estimated age at onset, genotype, their interaction on standardized clinical, cognitive, pathologic outcome measures the National Alzheimer's Coordinating Center...
The prokaryotic ubiquitin-like protein (Pup)-based proteasomal system in the pathogen Mycobacterium tuberculosis (Mtb) is essential for its survival a mammalian host. Pup ligase enzyme, PafA, conjugates to suite of proteins targeted degradation and necessary persistent infection by Mtb. We report design application fluorescent probes use elucidating mechanisms substrate recognition PafA. Our studies revealed that C-terminal 26 amino acid sequence minimal motif Specific hydrophobic residues...
A major problem in the treatment of cocaine addiction is high rates relapse. Relapse often provoked by acute reexposure to cocaine-associated cues or itself. The lateral habenula (LHb), an epithalamic nucleus, regulates midbrain dopaminergic systems that are known be involved taking and seeking behaviors. However, role this nucleus self-administration reinstatement has not been entirely parsed out. We used operant procedure explore effect Designer Receptors Exclusively Activated Drug...
Arterial stiffening has emerged as an important risk factor for Alzheimer's disease (AD) and related dementias. Carotid-femoral pulse wave velocity been proposed a non-invasive reproducible method to assess arterial stiffness. However, the association of with performance across multiple cognitive domains well interactions in vivo AD biomarkers apolipoprotein E (APOE) genotype received limited study.We studied 193 older adult volunteers (167 normal cognition 26 mild impairment) who underwent...
Although subjective cognitive decline (SCD) may be an early risk marker of Alzheimer's Disease (AD), research on SCD among Hispanics/Latinos/as/x (henceforth Latinos/as) living in the U.S. is lacking. We investigated if cross-sectional relationship self-reported with objective cognition varies as a function ethnic background (Latinos/as versus Non-Hispanic Whites [NHWs]). Secondary analyses conducted solely within Latino/a group informant reported associated and whether related to markers...
Blood phosphorylated tau (p-tau) biomarkers, including p-tau217, show high associations with Alzheimer's disease (AD) neuropathologic change and clinical stage. Certain plasma p-tau217 assays recognize forms additionally at threonine-212, but the contribution of p-tau212 alone to AD is unknown. We developed a blood-based immunoassay that specific without cross-reactivity p-tau217. Thereafter, we examined diagnostic utility p-tau212. In five cohorts (n=388 participants), showed performances...
<h3>Background and Objective</h3> Patients with dementia Lewy bodies perform worse than those Alzheimer disease (AD) on tests of visual perception, but the clinical utility these remains unknown because studies often had clinically diagnosed groups that may inadvertently cross-contaminate body (LBD) pure AD pathology, used experimental not easily adaptable for use, no way to examine relationships between severity LBD pathology degree cognitive impairment. Therefore, we sought determine...
Abstract Background Glial fibrillary acidic protein (GFAP) is an astrocytic marker that has been recently associated with fluid and imaging biomarkers of amyloid tau pathologies in the Alzheimer’s disease (AD) spectrum. Plasma GFAP also shown to be a strong indicator early brain amyloidosis preclinical AD. However, it remains confirmed how plasma associates neuropathological hallmarks AD which pathological entities are being reflected by this plasmatic marker. Method concentrations were...
The present study examined the effects of aging and CSF biomarkers Alzheimer's disease (AD) on ability to control production unexpected words in connected speech elicited by reading aloud. Fifty-two cognitively healthy participants aged 66-86 read aloud 6 paragraphs with 10 malapropisms including 5 content (e.g., "window cartons" that autocorrect errors curtains") function "thus concept" autocorrections "this concept") completed a battery neuropsychological tests standardized Stroop task....
The present study investigated cognitive mechanisms underlying the ability to stop "autocorrect" errors elicited by unexpected words in a read-aloud task, and utility of autocorrection for predicting Alzheimer's disease (AD) biomarkers.