A5101602346- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Amyotrophic Lateral Sclerosis Research
- Neurological disorders and treatments
- Dementia and Cognitive Impairment Research
- S100 Proteins and Annexins
- Advanced Neuroimaging Techniques and Applications
- Health Systems, Economic Evaluations, Quality of Life
- Cerebrovascular and genetic disorders
- Neurological Disorders and Treatments
- Botulinum Toxin and Related Neurological Disorders
- Neurogenetic and Muscular Disorders Research
- Advanced MRI Techniques and Applications
- Genetic Neurodegenerative Diseases
- Neurological diseases and metabolism
- Medical Imaging Techniques and Applications
- Autophagy in Disease and Therapy
- Memory and Neural Mechanisms
- Cerebral Palsy and Movement Disorders
- Neurological Disease Mechanisms and Treatments
- Lysosomal Storage Disorders Research
- Ginkgo biloba and Cashew Applications
- Aortic Disease and Treatment Approaches
- Viral Infectious Diseases and Gene Expression in Insects
- Traumatic Brain Injury Research
Denali Therapeutics (United States)
2022-2024
University of California, San Francisco
2005-2021
University Memory and Aging Center
2014-2020
Center for Neurosciences
2019
National Yang Ming Chiao Tung University
2018
Hope Center for Neurological Disorders
2017
University of California, Berkeley
2017
Johns Hopkins University
2017
Johns Hopkins Medicine
2017
Lawrence Berkeley National Laboratory
2017
Tau imaging with [ 18 F]flortaucipir predicts the severity and topography of subsequent MRI cortical atrophy in patients Alzheimer’s disease.
<h3>Importance</h3> The positron emission tomography (PET) tracer [<sup>18</sup>F]flortaucipir allows in vivo quantification of paired helical filament tau, a core neuropathological feature Alzheimer disease (AD), but its diagnostic utility is unclear. <h3>Objective</h3> To examine the discriminative accuracy for AD vs non-AD neurodegenerative disorders. <h3>Design, Setting, and Participants</h3> In this cross-sectional study, 719 participants were recruited from 3 dementia centers South...
Blood-based biomarkers for neurodegenerative conditions could improve diagnosis and treatment development. Neurofilament light chain (NfL), a marker of axonal injury, is elevated in cerebrospinal fluid (CSF) patients with progressive supranuclear palsy (PSP). The goal this study was to determine the diagnostic prognostic value plasma NfL PSP.Plasma measured ultrasensitive digital immunoassay-based technology at baseline 1-year follow-up pilot cohort 15 PSP 12 healthy controls, validation 147...
The botulinum neurotoxins (BoNTs) are category A biothreat agents which have been the focus of intensive efforts to develop vaccines and antibody-based prophylaxis treatment. Such approaches must take into account extensive BoNT sequence variability; seven serotypes differ by up 70% at amino acid level. Here, we analyzed 49 complete published sequences BoNTs show that all toxins also exhibit variability within ranging between 2.6 31.6%. To determine impact such differences on immune...
Objective 18 F‐flortaucipir (formerly F‐AV1451 or F‐T807) binds to neurofibrillary tangles in Alzheimer disease, but tissue studies assessing binding tau aggregates progressive supranuclear palsy (PSP) have yielded mixed results. We compared vivo uptake patients meeting clinical research criteria for PSP (n = 33) normal controls 46) and Parkinson disease (PD; n 26). Methods Participants underwent magnetic resonance imaging positron emission tomography amyloid‐β ( 11 C‐PiB F‐florbetapir)...
The tau positron emission tomography (PET) ligand 18F-flortaucipir binds to paired helical filaments of in aging and Alzheimer's disease (AD), but its utility detecting aggregates frontotemporal dementia (FTD) is uncertain. We performed imaging patients with the FTD syndromes (n = 45): nonfluent variant primary progressive aphasia (nfvPPA) 11), corticobasal syndrome (CBS) 10), behavioral (bvFTD) semantic (svPPA) 2) associated pathogenic genetic mutations microtubule-associated protein (MAPT)...
<h3>Objective</h3> To assess the relationships between fluid and imaging biomarkers of tau pathology compare their diagnostic utility in a clinically heterogeneous sample. <h3>Methods</h3> Fifty-three patients (28 with clinical Alzheimer disease [AD] 25 non-AD neurodegenerative diagnoses) underwent β-amyloid (Aβ) ([<sup>18</sup>F]AV1451) PET lumbar puncture. CSF (Aβ<sub>42</sub>, total [t-tau], phosphorylated [p-tau]) were measured by multianalyte immunoassay (AlzBio3). Receiver operator...
<h3>Importance</h3> Basket-design clinical trials that allow investigation of treatment effects on different syndromes share the same molecular pathophysiology have not previously been attempted in neurodegenerative disease. <h3>Objective</h3> To assess safety, tolerability, and pharmacodynamics microtubule stabilizer TPI-287 (abeotaxane) Alzheimer disease (AD) or 4-repeat tauopathies (4RT) progressive supranuclear palsy (PSP) corticobasal syndrome (CBS). <h3>Design, Setting,...
Abstract Introduction Differential patterns of brain atrophy on structural magnetic resonance imaging (MRI) revealed four reproducible subtypes Alzheimer's disease (AD): (1) “typical”, (2) “limbic‐predominant”, (3) “hippocampal‐sparing”, and (4) “mild atrophy”. We examined the neurobiological characteristics clinical progression these atrophy‐defined subtypes. Methods The were replicated using a clustering method MRI data in 260 amyloid‐β‐positive patients with mild cognitive impairment or...
Abstract Background The trans-neuronal propagation of tau has been implicated in the progression tau-mediated neurodegeneration. There is critical knowledge gap understanding how released and transmitted, that dysregulated diseases. Previously, we reported lysine acetyltransferase p300/CBP acetylates regulates its degradation toxicity. However, whether involved regulation secretion unknown. Method We investigated relationship between activity, autophagy-lysosomal pathway (ALP) mouse models...
To determine the ability of CSF biomarkers to predict disease progression in progressive supranuclear palsy (PSP).We compared baseline β-amyloid1-42, tau, phosphorylated tau 181 (p-tau), and neurofilament light chain (NfL) concentrations, measured by INNO-BIA AlzBio3 or ELISA, 52-week changes clinical (PSP Rating Scale [PSPRS] Schwab England Activities Daily Living [SEADL]), neuropsychological, regional brain volumes on MRI using linear mixed effects models controlled for age, sex, severity,...
To characterize individual and group-level neuroimaging findings in patients at risk for Chronic Traumatic Encephalopathy (CTE). Eleven male meeting criteria Syndrome (TES, median age: 64) underwent neurologic evaluation, 3-Tesla MRI, PET with [18F]-Flortaucipir (FTP, tau-PET) [11C]-Pittsburgh compound B (PIB, amyloid-PET). Six [18F]-Fluorodeoxyglucose-PET (FDG, glucose metabolism). We assessed imaging the patient level, comparisons modality-specific groups of cognitively normal older adults...
Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are both 4 microtubule binding repeat tauopathy related disorders. Clinical trials need new biomarkers to assess the effectiveness of tau-directed therapies. This study investigated regional distribution longitudinal diffusion tensor imaging changes, measured by fractional anisotropy, radial axial diffusivity over 6 months median interval, in 23 normal control subjects, 35 patients with PSP, 25 CBS. A mixed-effects...
Progressive supranuclear palsy (PSP) is a neurodegenerative disease without approved therapies, and therapeutics are often tried off-label in the hope of slowing progression. Results from these experiences seldom shared, which limits evidence-based knowledge to guide future treatment decisions.
Analytical methods optimized for micellar F5cys-MP-PEG(2000)-DPSE protein-lipopolymer conjugate are presented. The apparent micelle molecular weight, determined by size exclusion chromatography, ranged from 330 to 960 kDa. F5cys antibody and melting points, differential scanning calorimetry, were near 82 degrees C. Traditional characterizing monodisperse protein species inapplicable analysis. isoelectric point of (9.2) the (8.9) capillary focusing (cIEF) after addition zwitterionic detergent...
Abstract Background Frontotemporal dementia (FTD) is the most common cause of early-onset with 10-20% cases caused by mutations in one three genes: GRN , C9orf72 or MAPT . To effectively develop therapeutics for FTD, identification and characterization biomarkers to understand disease pathogenesis evaluate impact specific therapeutic strategies on target biology as well underlying pathology are essential. Moreover, tracking longitudinal changes these throughout progression crucial discern...
Abstract Introduction Frontotemporal lobar degeneration–causing mutations in the progranulin ( GRN ) gene reduce protein (PGRN) levels, suggesting that restoring PGRN mutation carriers may be therapeutic. Nimodipine, a Food and Drug Administration–approved blood‐brain barrier‐penetrant calcium channel blocker, increased levels PGRN‐deficient murine models. We sought to assess safety tolerability of oral nimodipine human carriers. Methods performed an open‐label, 8‐week, dose‐finding, phase 1...
<h3>Objective:</h3> DNL343 is being investigated as a potential therapeutic agent for Amyotrophic Lateral Sclerosis (ALS). <h3>Background:</h3> ALS fatal neurodegenerative disease with TDP-43 inclusion pathology in 95% of patients. Chronic activation the integrated stress response (ISR) may contribute to by blocking translation, altering RNA and endosomal trafficking, increasing formation TDP-43-containing granules. small molecule that activates key ISR regulator, eIF2B, which inhibits...
Background:The International Working Group (IWG) recently proposed the revised diagnostic criteria for Alzheimer's disease (AD) to define and refine several types of AD, reclassify AD-related biomarkers into progression markers, but its performance is not known. Objective:This study was designed describe application IWG in Disease Neuroimaging Initiative (ADNI) dataset, ascertain whether markers show significant differences their relationships AD severity progression. Methods:Based on...