A5039207487- Alzheimer's disease research and treatments
- Parkinson's Disease Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Long-Term Effects of COVID-19
- Dementia and Cognitive Impairment Research
- Olfactory and Sensory Function Studies
- RNA Research and Splicing
- Neurological disorders and treatments
- Molecular Biology Techniques and Applications
- COVID-19 Clinical Research Studies
- Neurogenesis and neuroplasticity mechanisms
- RNA and protein synthesis mechanisms
- Neuroscience and Neuropharmacology Research
- Advanced Neuroimaging Techniques and Applications
- Ginkgo biloba and Cashew Applications
- RNA modifications and cancer
- Botulinum Toxin and Related Neurological Disorders
- Neurological Disease Mechanisms and Treatments
- Biochemical Analysis and Sensing Techniques
- Mental Health and Patient Involvement
- Dysphagia Assessment and Management
- Ocular Oncology and Treatments
- Palliative Care and End-of-Life Issues
- Restless Legs Syndrome Research
- Autopsy Techniques and Outcomes
Banner Sun Health Research Institute
2016-2025
Newcastle University
2023-2025
Birmingham Children's Hospital
2024
Alzheimer's Association
2023
Banner Alzheimer’s Institute
2023
The Ohio State University
2009
University of Sheffield
2002
Background: Conflicting results from studies of Lewy-type α−synucleinopathy (LTS) in colonic biopsies subjects with Parkinson's disease (PD) prompted a two-part multicenter assessment. The first assessment, now published (Acta Neuropathol Commun 4 : 35, 2016), examined archived and found that none the tested methods was adequately sensitive or specific. Objective: As amount nervous tissue typical may be insufficient, clinical diagnosis PD not completely accurate, objective current study to...
The coronavirus SARS-CoV-2 (SCV2) causes acute respiratory distress, termed COVID-19 disease, with substantial morbidity and mortality. As SCV2 is related to previously-studied coronaviruses that have been shown the capability for brain invasion, it seems likely may be able do so as well. To date, although there many clinical autopsy-based reports describe a broad range of SCV2-associated neurological conditions, unclear what fraction these due direct CNS invasion versus indirect effects...
Background: Braak and others have proposed that Lewy-type α-synucleinopathy in Parkinson’s disease (PD) may arise from an exogenous pathogen passes across the gastric mucosa then is retrogradely transported up vagus nerve to medulla. Objective: We tested this hypothesis by immunohistochemically staining, with a method specific for p-serine 129 α-synuclein (pSyn), stomach tissue autopsy series of 111 normal elderly subjects, 33 incidental Lewy body (ILBD) 53 PD. Methods: Vagus samples were...
Extensive research strongly suggests that amyloid beta (Aβ) aggregates in the brain have a central role Alzheimer's disease (AD) pathogenesis. Pathological Aβ deposition is likely due to an altered balance between overproduction and elimination. Rodent studies suggested liver has major degradation. It possible alterations of function could affect levels through changes blood concentration. In this study, we hypothesized hepatic degradation be impaired AD subjects. To test our hypothesis,...
Brains of 42 COVID-19 decedents and 107 non-COVID-19 controls were studied. RT-PCR screening 16 regions from 20 autopsies found SARS-CoV-2 E gene viral sequences in 7 (2.5% 320 samples), concentrated 4/20 subjects (20%). Additional olfactory bulb (OB), amygdala (AMY) entorhinal area for E, N1, N2, RNA-dependent RNA polymerase, S detected one or more these OB 8/21 (38%). It is uncertain whether represent viable virus. Significant histopathology was limited to 2/42 cases (4.8%), with a large...
Neuropathology has demonstrated a high rate of comorbid pathology in dementia due to Alzheimer's disease (ADD). The most common major comorbidity is Lewy body (LBD), either as with bodies (AD-DLB) or (AD-LB), the latter representing subjects ADD and LBD not meeting neuropathological distribution density thresholds for DLB. Although it been established that undifferentiated have more rapid cognitive decline than those alone, still unknown whether AD-LB subjects, who represent majority...
Synaptic transmission is essential for nervous system function and the loss of synapses a known major contributor to dementia. Alzheimer’s disease dementia (ADD) characterized by synaptic in mesial temporal lobe cerebral neocortex, both which are brain areas associated with memory cognition. The association ADD was established late 1980s, it has been estimated that 30–50% neocortical protein lost ADD, but there not yet quantitative profiling different proteins regions from same individuals....
Abstract Cognitive Stimulation Therapy (CST) is a group psychosocial intervention for people with mild-to-moderate dementia. Despite evidence supporting its effectiveness, cost-effectiveness, and cultural adaptation internationally, CST has yet to be implemented in routine practice outside of the UK. This study consisted multiple phases. In first phase, we engaged stakeholders explore barriers facilitators implementation Tanzania. second developed strategies. third tested these strategies...
Immunohistochemical (IHC) α-synuclein (Asyn) pathology in peripheral biopsies may be a biomarker of Parkinson disease (PD). The multi-center Systemic Synuclein Sampling Study (S4) is evaluating IHC Asyn within skin, colon and submandibular gland from 60 PD 20 control subjects. being evaluated by blinded panel specially trained neuropathologists. Preliminary work assessed 2 candidate immunoperoxidase methods using set autopsy-derived sections formalin-fixed, paraffin-embedded blocks the 3...
Many subjects with neuropathologically-confirmed dementia Lewy bodies (DLB) are never diagnosed during life, instead being categorized as Alzheimer's disease (ADD) or unspecified dementia. Unrecognized DLB therefore is a critical impediment to clinical studies and treatment trials of both ADD DLB. There that suggest olfactory function tests may be able distinguish from ADD, but few these had neuropathological confirmation diagnosis. We compared University Pennsylvania Smell Identification...
Cerebral white matter rarefaction (CWMR) was considered by Binswanger and Alzheimer to be due cerebral arteriolosclerosis. Renewed attention came with CT MR brain imaging, neuropathological studies finding a high rate of CWMR in disease (AD). The relative contributions cerebrovascular AD are still uncertain. In 1181 autopsies the Arizona Study Aging Neurodegenerative Disorders (AZSAND), large-format sections were used grade determine its vascular neurodegenerative correlates. Almost all...
ABSTRACT Astrocytes have multiple crucial roles, including maintaining brain homeostasis and synaptic function, performing phagocytic clearance responding to injury repair. It has been suggested that astrocyte performance is progressively impaired with aging, leading imbalances in the brain’s internal milieu eventually impact neuronal function leads neurodegeneration. Until now most of evidence astrocytic dysfunction aging come from experiments done whole tissue homogenates, astrocytes...
Astrocytes have multiple crucial roles, including maintaining brain homeostasis and synaptic function, performing phagocytic clearance, responding to injury repair. It has been suggested that astrocyte performance is progressively impaired with aging, leading imbalances in the brain's internal milieu eventually impact neuronal function lead neurodegeneration. Until now, most evidence of astrocytic dysfunction aging come from experiments done whole tissue homogenates, astrocytes collected by...
In the early days of 2019 coronavirus disease (COVID-19) pandemic, there were few published guidelines for safely performing autopsies infected individuals. The limited information relied on assumptions that risks would be similar to those other primarily respiratory infections, but remained a considerable number uncertainties, particularly in regard potential aerosol transmission. Despite these novel risks, it was crucial our program quickly gain more knowledge about this new pathogen by...
The determination of RNA integrity is a critical quality assessment tool for gene expression studies where the experiment’s success highly dependent on sample quality. Since its introduction in 1999, gold standard scientific community has been Agilent 2100 Bioanalyzer’s number (RIN), which uses 1–10 value system, from 1 being most degraded, to 10 intact. In 2015, launched 4200 TapeStation’s RIN equivalent, and reported strong correlation r2 0.936 median error < ±0.4 units. To evaluate...
The olfactory bulb is involved early in the pathophysiology of Parkinson's disease (PD), which consistent with onset dysfunction. Identifying molecular mechanisms through PD affects could lead to a better understanding and etiology dysfunction PD. We specifically aimed assess gene expression changes, affected pathways co-expression network by whole transcriptomic profiling subjects clinicopathologically defined Bulk RNA sequencing was performed on frozen human bulbs 20 controls without...
In this study we conducted RNA sequencing on two brain regions (olfactory bulb and amygdala) from subjects who died COVID-19 or of other causes. We found several-fold more transcriptional changes in the olfactory than amygdala, consistent with our own work that others indicating may be initial most common region infected. To some extent results converge pseudotime analysis towards processes shared between regions, possibly induced by systemic immune reaction following SARS-CoV-2 infection....
To determine prevalence of REM sleep behavior disorder (RBD) [prodromal Lewy body disease] in Sun City, Arizona.We attempted, by telephone and mail, a survey using the RBD single item question for probable (pRBD) Innsbruck Inventory. Individuals answering "yes" to 4/5 Inventory questions were considered have high likelihood (HL-RBD.).Response rate was 484/3000 individuals contacted (16%), mean age 78; 48 (9.9%) endorsed pRBD RBD1Q; 16 (3.3%) had HL-pRBD. Prevalence idiopathic cases (without...
ABSTRACT Braak and others have proposed that Lewy-type α-synucleinopathy (aSyn) in Parkinson’s disease (PD) may arise from an exogenous pathogen passes across the gastric mucosa then is retrogradely transported up vagus nerve to medulla. We tested this “body-first” hypothesis by immunohistochemically staining stomach tissue autopsy series of 111 normal elderly subjects (no brain aSyn), 33 with incidental Lewy body (ILBD) (brain aSyn without clinical parkinsonism or dementia) 53 PD. Median...
Comorbid Lewy body pathology is very common in Alzheimer's disease and may confound clinical trial design, yet there no vivo test to identify patients with this. Tissue (and/or radioligand imaging) studies have shown cardiac sympathetic denervation Parkinson's dementia bodies, but this has not been explored subjects bodies meeting clinicopathological criteria. To determine if show denervation, we analysed epicardial myocardial tissue from autopsy-confirmed cases using tyrosine hydroxylase...
Abstract There has been a markedly renewed interest in factors associated with pneumonia, leading cause of death worldwide, due to its frequent concurrence pandemics influenza and Covid-19 disease. Reported predisposing both bacterial pneumonia pandemic viral lower respiratory infections are wintertime occurrence, older age, obesity, pre-existing cardiopulmonary conditions diabetes. Also implicated age-related neurodegenerative diseases that parkinsonism dementia. We investigated the...
Introduction: Tanzania is a low-income country with an increasing prevalence of dementia, which provides challenges for the existing healthcare system. People dementia often don’t receive formal diagnosis, and lack healthcare, are predominantly supported by family relatives. There very few published data relating to lived experiences people in Tanzania. This study aimed understand their caregivers’ living perceived needs dementia. Methods: Qualitative, semi-structured interviews were...
Abstract Stroke is one of the most serious complications Covid-19 disease but it still unclear whether stroke more common with pneumonia as compared to non-Covid-19 pneumonia. We investigated concurrence rate autopsy-confirmed acute brain ischemia, infarction and hemorrhage autopsy-proven non-Covid in consecutive autopsies Arizona Study Aging Neurodegenerative Disorders (AZSAND), a longitudinal clinicopathological study normal aging neurodegenerative diseases. Of 691 subjects mean age 83.4...
The spread of neurofibrillary tau pathology in Alzheimer disease (AD) mostly follows a stereotypical pattern topographical progression but atypical patterns associated with interhemispheric asymmetry have been described. Because histopathological studies that used bilateral sampling are limited, this study aimed to assess differences and the presence topographically cortical spreading patterns. Immunohistochemical staining for detection was performed 23 regions interest 57 autopsy cases...