A5089194486- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Neuroscience and Neuropharmacology Research
- Parkinson's Disease Mechanisms and Treatments
- SARS-CoV-2 detection and testing
- Neurological Disease Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- SARS-CoV-2 and COVID-19 Research
- Sleep and Wakefulness Research
- Cholinesterase and Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Cerebrovascular and genetic disorders
- Advanced biosensing and bioanalysis techniques
- Biosensors and Analytical Detection
- S100 Proteins and Annexins
- Amyotrophic Lateral Sclerosis Research
- Health, Environment, Cognitive Aging
- Aortic aneurysm repair treatments
- Genetic Neurodegenerative Diseases
- Moyamoya disease diagnosis and treatment
- Bioinformatics and Genomic Networks
- Dental Research and COVID-19
- COVID-19 epidemiological studies
- Nerve injury and regeneration
- Functional Brain Connectivity Studies
University Memory and Aging Center
2017-2025
University of California, San Francisco
2016-2025
University of California, Berkeley
2016-2025
Innovative Genomics Institute
2020-2025
Integra (United States)
2020-2025
Center for Neurosciences
2020-2023
Neurosciences Institute
2023
Lund University
2022
Skåne University Hospital
2022
Amsterdam Neuroscience
2022
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...
Aims Hyperphosphorylated tau neuronal cytoplasmic inclusions (ht‐ NCI ) are the best protein correlate of clinical decline in Alzheimer's disease ( AD ). Qualitative evidence identifies ht‐ accumulating isodendritic core before entorhinal cortex. Here, we used unbiased stereology to quantify burden locus coeruleus (LC) and dorsal raphe nucleus (DRN), aiming characterize impact pathology these nuclei with a focus on early stages. Methods We utilized sample 48 well‐characterized subjects...
Clarifying the relationships between neuropsychiatric symptoms and Alzheimer’s disease (AD)-related pathology may open avenues for effective treatments. Here, we investigate odds of developing across increasing burdens neurofibrillary tangle amyloid-β pathology. Participants who passed away 2004 2014 underwent comprehensive neuropathologic evaluation at Biobank Aging Studies from Faculty Medicine University São Paulo. Postmortem interviews with reliable informants were used to collect...
To determine how fully automated Elecsys CSF immunoassays for β-amyloid (Aβ) and tau biomarkers an ultrasensitive Simoa assay neurofilament light chain (NFL) correlate with neuropathologic changes of Alzheimer disease (AD) frontotemporal lobar degeneration (FTLD).We studied 101 patients antemortem neuropathology data. samples were collected a mean 2.9 years before death (range 0.2-7.5 years). was analyzed Aβ40, Aβ42, total (T-tau), phosphorylated at amino acid residue 181 (P-tau), P-tau/Aβ42...
Abstract Introduction Sleep‐wake disturbances are a common and early feature in Alzheimer's disease (AD). The impact of tau pathology wake‐promoting neurons (WPNs) remains unclear. Methods We performed stereology postmortem brains from AD individuals healthy controls to identify quantitative differences morphological metrics WPNs. Progressive supranuclear palsy (PSP) corticobasal degeneration were included as disease‐specific controls. Results three nuclei studied accumulate considerable...
Abstract The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau‐associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction cortical lesions. Accumulating evidence supports role behavioral neuropsychiatric manifestations featured AD. Experimental studies even suggest that AD‐associated drives brain neuroinflammatory status contributes to...
Abstract Enlarged perivascular spaces have been previously reported in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, but their significance pathophysiology remains unclear. We investigated associations of white matter enlarged classical imaging measures, cognitive measures plasma proteins to better understand what represent leukoencephalopathy whether radiographic would be value future therapeutic discovery studies for leukoencephalopathy....
The brainstem nuclei of the reticular formation (RF) are critical for regulating homeostasis, behavior, and cognition. RF degenerates in tauopathies including Alzheimer disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD). Although burden phopho-tau inclusion is high across these diseases, suggesting a similar vulnerability pattern, distinct RF-associated clinical phenotype diseases indicates opposite. To compare patterns selective to tauopathies, we analyzed 5...
Alzheimer's disease (AD) and primary age-related tauopathy (PART) both harbor 3R/4R hyperphosphorylated-tau (p-tau)-positive neurofibrillary tangles (NFTs) but differ in the spatial p-tau development hippocampus.
The high proportion of transmission events derived from asymptomatic or presymptomatic infections make SARS-CoV-2, the causative agent in COVID-19, difficult to control through traditional non-pharmaceutical interventions (NPIs) symptom-based isolation and contact tracing. As a consequence, many US universities developed surveillance testing labs, augment NPIs outbreaks on campus throughout 2020–2021 academic year (AY); several those labs continue support efforts AY2021–2022. At height...
<h3>Objectives</h3> Alzheimer disease (AD) shows a broad array of clinical presentations, but the mechanisms underlying these phenotypic variants remain elusive. Aging-related astrogliopathy (ARTAG) is relatively recent term encompassing tau deposition in astroglia outside range traditional tauopathies. White matter thorn-shaped astrocyte (WM-TSA) clusters, specific ARTAG subtype, has been associated with atypical language presentation AD small study lacking replication. To interrogate...
Rates of cognitive decline in Alzheimers disease (AD) are extremely heterogeneous, with ages symptom onset ranging from age 40 to 100 years and conversion mild impairment AD dementia taking 2 20 years. Development biomarkers for amyloid-beta (AB) tau protein aggregates, the hallmark pathologies AD, have improved patient monitoring/stratification drug development, but they still only explain 40% variance (CI) AD. To discover additional molecular drivers dementia, we perform cerebrospinal...
INTRODUCTION: The cellular origins of pituitary neuroendocrine tumors (PitNETs) are uncertain, positing that PitNETs may originate from differentiated cells or adult stem cells. Understanding these is essential for developing targeted therapies aimed at tumor-initiating cells, thereby enhancing treatment efficacy. METHODS: We conducted single-nucleus sequencing on approximately half a million creating the largest database to date. This included samples two non-tumor postmortem pituitaries...
Alzheimer's disease (AD) selectively affects certain brain regions, yet the mechanisms of selective vulnerability remain poorly understood. The neuromodulatory subcortical system, which includes nuclei exhibiting a range and resilience to AD-type degeneration, presents framework for uncovering these mechanisms. We leveraged transcriptomics immunohistochemistry in paired samples from human post mortem tissue representing vulnerable resilient region-the locus coeruleus (LC) substantia nigra...
Rates of cognitive decline in Alzheimer's disease (AD) are extremely heterogeneous. Although biomarkers for amyloid-beta (Aβ) and tau proteins, the hallmark AD pathologies, have improved pathology-based diagnosis, they explain only 20-40% variance AD-related impairment (CI). To discover novel CI AD, we performed cerebrospinal fluid (CSF) proteomics on 3,397 individuals from six major prospective case-control cohorts. Synapse proteins emerged as strongest correlates CI, independent Aβ tau....
Tau truncation (tr-tau) by active caspase-6 (aCasp-6) generates tau fragments that may be toxic. Yet the relationship between aCasp-6, different forms of tr-tau and hyperphosphorylated (p-tau) accumulation in human brains with Alzheimer's disease (AD) other tauopathies remains unclear.We generated two neoepitope monoclonal antibodies against sites (D402 D13) targeted aCasp-6. Then, we used five-plex immunofluorescence to quantify neuronal astroglial burden tr-tau, p-tau their co-occurrence...
Regular surveillance testing of asymptomatic individuals for SARS-CoV-2 has been center to outbreak prevention on college and university campuses. Here we describe the voluntary saliva program instituted at University California, Berkeley during an early period pandemic in 2020. The was administered as a research study ahead clinical implementation, enabling us launch while continuing optimize assay. Results both protocol itself participants’ experience show how succeeded providing routine,...