A5003878251- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Parkinson's Disease Mechanisms and Treatments
- Amyotrophic Lateral Sclerosis Research
- Sleep and Wakefulness Research
- Neurological Disease Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Functional Brain Connectivity Studies
- Advanced Neuroimaging Techniques and Applications
- Neuroscience and Neuropharmacology Research
- Cerebrovascular and genetic disorders
- Neurological diseases and metabolism
- Neurological disorders and treatments
- Cholinesterase and Neurodegenerative Diseases
- Neurobiology of Language and Bilingualism
- Mitochondrial Function and Pathology
- S100 Proteins and Annexins
- Genetic Neurodegenerative Diseases
- Sleep and related disorders
- Memory and Neural Mechanisms
- Circadian rhythm and melatonin
- Cerebrovascular and Carotid Artery Diseases
- Neurological Disorders and Treatments
- Cell Image Analysis Techniques
- Health, Environment, Cognitive Aging
University of California, San Francisco
2016-2025
Universidade de São Paulo
2016-2025
University Memory and Aging Center
2016-2025
Global Brain Health Institute
2018-2025
University of San Francisco
2014-2024
Universidade Cidade de São Paulo
2024
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
2013-2024
Alzheimer’s Disease Neuroimaging Initiative
2007-2024
The University of Texas Health Science Center at Houston
2024
University of Florida
2024
Abstract The human brain is often considered to be the most cognitively capable among mammalian brains and much larger than expected for a mammal of our body size. Although number neurons generally assumed determinant computational power, despite widespread quotes that contains 100 billion ten times more glial cells, absolute cells in remains unknown. Here we determine these numbers by using isotropic fractionator compare them with values human‐sized primate. We find adult male on average...
Prions are proteins that adopt alternative conformations become self-propagating; the PrP Sc prion causes rare human disorder Creutzfeldt–Jakob disease (CJD). We report here multiple system atrophy (MSA) is caused by a different composed of α-synuclein protein. MSA slowly evolving characterized progressive loss autonomic nervous function and often signs parkinsonism; neuropathological hallmark glial cytoplasmic inclusions consisting filaments α-synuclein. To determine whether forms prions,...
To elucidate the role of Tau isoforms and post-translational modification (PTM) stoichiometry in Alzheimer's disease (AD), we generated a high-resolution quantitative proteomics map 95 PTMs on multiple isolated from postmortem human tissue 49 AD 42 control subjects. Although PTM maps reveal heterogeneity across subjects, subset display high occupancy frequency for AD, suggesting importance disease. Unsupervised analyses indicate that occur an ordered manner, leading to aggregation. The...
A 'frontal variant of Alzheimer's disease' has been described in patients with predominant behavioural or dysexecutive deficits caused by disease pathology. The description this rare phenotype limited to case reports and small series, many clinical, neuroimaging neuropathological characteristics are not well understood. In retrospective study, we included 55 a behavioural-predominant presentation (behavioural disease) diagnosis high-likelihood (n = 17) and/or biomarker evidence pathology...
Amyloid-β, a hallmark of Alzheimer’s disease, begins accumulating up to two decades before the onset dementia, and can be detected in vivo applying amyloid-β positron emission tomography tracers such as carbon-11-labelled Pittsburgh compound-B. A variety thresholds have been applied literature define compound-B positivity, but ability these detect early deposition is unknown, validation studies comparing post-mortem amyloid burden are lacking. In this study we first derived for positivity...
To characterize in vivo signatures of pathological diagnosis a large cohort patients with primary progressive aphasia (PPA) variants defined by current diagnostic classification.Extensive clinical, cognitive, neuroimaging, and neuropathological data were collected from 69 sporadic PPA, divided into 29 semantic (svPPA), 25 nonfluent (nfvPPA), 11 logopenic (lvPPA), 4 mixed PPA. Patterns gray matter (GM) white (WM) atrophy at presentation assessed tested as predictors using support vector...
Alzheimer's disease (AD) progression follows a specific spreading pattern, emphasizing the need to characterize those brain areas that degenerate first. The brainstem's locus coeruleus (LC) is first area develop neurofibrillary changes (neurofibrillary tangles [NFTs]).The methods include unbiased stereological analyses in human brainstems estimate LC volume and neuronal population controls individuals across all AD stages.As Braak stage increases by 1 unit, decreases 8.4%. Neuronal loss...
To compare the diagnostic performance of PET with amyloid ligand Pittsburgh compound B (PiB-PET) to fluorodeoxyglucose (FDG-PET) in discriminating between Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD).Patients meeting clinical criteria for AD (n = 62) FTLD 45) underwent PiB FDG-PET. scans were classified as positive or negative by 2 visual raters blinded diagnosis, using a quantitative threshold derived from controls 25). FDG visually rated consistent FTLD,...
Accurately predicting the underlying neuropathological diagnosis in patients with behavioural variant frontotemporal dementia (bvFTD) poses a daunting challenge for clinicians but will be critical success of disease-modifying therapies. We sought to improve pathological prediction by exploring clinicopathological correlations large bvFTD cohort. Among 438 whom was either top or an alternative possible clinical diagnosis, 117 had available autopsy data, including 98 primary lobar degeneration...
Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are among the human synucleinopathies, which show alpha-synuclein immunoreactive neuronal and/or glial aggregations progressive loss in selected brain regions (eg, substantia nigra, ventral tegmental area, pedunculopontine nucleus). Despite several studies about brainstem pathologies PD DLB, there is currently no detailed information available regarding presence of inclusions (i) cranial nerve, precerebellar, vestibular oculomotor...
Cerebrospinal fluid (CSF) neurofilament light chain (NfL) concentration is elevated in neurological disorders, including frontotemporal degeneration (FTD). We investigated the clinical correlates of CSF NfL levels FTD.CSF NfL, amyloid-β1-42 (Aβ42), tau, and phosphorylated tau concentrations were compared 47 normal controls (NC), 8 asymptomatic gene carriers (NC2) FTD-causing mutations, 79 FTD (45 behavioral variant dementia [bvFTD], 18 progressive nonfluent aphasia [PNFA], 16 semantic [SD]),...
We sought to establish the relationships between standard postmortem measures of AD neuropathology and antemortem [11C]PIB-positron emission tomography ([11C]PIB-PET) analyzed with Centiloid (CL) method, a standardized scale for Aβ-PET quantification.Four centers contributed 179 participants encompassing broad range clinical diagnoses, PET data, autopsy findings.CL values increased each CERAD neuritic plaque score increment (median -3 CL no plaques 92 frequent plaques) nonlinearly Thal Aβ...
Activation of microglia is a prominent pathological feature in tauopathies, including Alzheimer's disease. How activation contributes to tau toxicity remains largely unknown. Here we show that nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB) signaling, by tau, drives microglial-mediated propagation and toxicity. Constitutive microglial NF-κB exacerbated, while inactivation diminished, seeding spreading young PS19 mice. Inhibition enhanced the retention reduced release...
Histopathological studies in Alzheimer's disease (AD) suggest severe and region-specific neurodegeneration of the basal forebrain cholinergic system (BFCS). Here, we studied between-center reliability diagnostic accuracy MRI-based BFCS volumetry a large multicenter data set, including participants with prodromal (n = 41) or clinically manifest AD 134) 148 cognitively healthy controls. Atrophy was determined using voxel-based region-of-interest based analyses high-dimensionally normalized MRI...