David J. Irwin
A5081337965- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Parkinson's Disease Mechanisms and Treatments
- Amyotrophic Lateral Sclerosis Research
- Advanced Neuroimaging Techniques and Applications
- Neurobiology of Language and Bilingualism
- Neurological diseases and metabolism
- Functional Brain Connectivity Studies
- Neurological disorders and treatments
- Language Development and Disorders
- Neurogenetic and Muscular Disorders Research
- Genetic Neurodegenerative Diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Cerebral Palsy and Movement Disorders
- Advanced MRI Techniques and Applications
- Cholinesterase and Neurodegenerative Diseases
- Neurological Disease Mechanisms and Treatments
- Botulinum Toxin and Related Neurological Disorders
- S100 Proteins and Annexins
- Prion Diseases and Protein Misfolding
- Health, Environment, Cognitive Aging
- Voice and Speech Disorders
- Medical Image Segmentation Techniques
- Genomics and Rare Diseases
- Health Systems, Economic Evaluations, Quality of Life
University of Pennsylvania
2016-2025
California University of Pennsylvania
2019-2025
Northwestern University
2024
Indiana University – Purdue University Indianapolis
2024
Inha University
2024
Penn Center for AIDS Research
2014-2024
VIB-UAntwerp Center for Molecular Neurology
2024
University of Antwerp
2024
University of California, Los Angeles
2020-2024
Philadelphia University
2013-2024
Background: PSP is a neuropathologically defined disease entity. Clinical diagnostic criteria, published in 1996 by the National Institute of Neurological Disorders and Stroke/Society for PSP, have excellent specificity, but their sensitivity limited variant syndromes with presentations other than Richardson's syndrome. Objective: We aimed to provide an evidence- consensus-based revision clinical criteria PSP. Methods: searched PubMed, Cochrane, Medline, PSYCInfo databases articles English...
Objective To see whether the distribution patterns of phosphorylated 43kDa TAR DNA‐binding protein (pTDP‐43) intraneuronal inclusions in amyotrophic lateral sclerosis (ALS) permit recognition neuropathological stages. Methods pTDP‐43 immunohistochemistry was performed on 70μm sections from ALS autopsy cases (N = 76) classified by clinical phenotype and genetic background. Results with lowest burden pathology were characterized lesions agranular motor cortex, brainstem nuclei cranial nerves...
Lewy bodies commonly occur in Alzheimer's disease, and disease pathology is frequent body diseases, but the burden of co-pathologies across neurodegenerative diseases unknown. We assessed extent tau, amyloid-β, α-synuclein TDP-43 proteinopathies 766 autopsied individuals representing a broad spectrum clinical disease. interrogated pathological (n = 247); other tauopathies 95) including Pick's corticobasal progressive supranuclear palsy; synucleinopathies 164) multiple system atrophy disease;...
Abstract Objective: A study was undertaken to examine the neuropathological substrates of cognitive dysfunction and dementia in Parkinson disease (PD). Methods: One hundred forty patients with a clinical diagnosis PD either normal cognition or onset 2 more years after motor symptoms (PDD) were studied. Patients Lewy bodies excluded. Autopsy records genetic data semiquantitative scores for burden neurofibrillary tangles, senile plaques, (LBs), neurites (LNs) other pathologies used develop...
<h3>Importance</h3> We observed a significant correlation between cerebrospinal fluid (CSF) levels of tau proteins and α-synuclein, but not β-amyloid 1-42 (Aβ1-42), lower concentration CSF biomarkers, as compared with healthy controls, in cohort entirely untreated patients Parkinson disease (PD) at the earliest stage studied so far. <h3>Objective</h3> To evaluate baseline characteristics relationship to clinical features biomarkers (Aβ1-42, total [T-tau], phosphorylated threonine 181...
<h3>Objective</h3>To test for an association between the apolipoprotein E (APOE) ϵ4 allele and dementias with synucleinopathy.<h3>Design</h3>Genetic case-control study.<h3>Setting</h3>Academic research.<h3>Patients</h3>Autopsied subjects were classified into 5 categories: dementia high-level Alzheimer disease (AD) neuropathologic changes (NCs) but without Lewy body (LBD) NCs (AD group; n = 244), LBDNCs ADNCs (LBD-AD 224), no or low levels of (pure DLB [pDLB] 91), Parkinson (PDD) (n 81),...
Importance Positron emission tomography (PET) may increase the diagnostic accuracy and confirm underlying neuropathologic changes of Alzheimer disease (AD). Objective To determine antemortem [ 18 F]flortaucipir PET images for predicting presence AD-type tau pathology at autopsy. Design, Setting, Participants This study (A16 primary cohort) was conducted from October 2015 to June 2018 28 sites (27 in US 1 Australia). Individuals with a terminal illness who were older than 50 years had...
Progressive supranuclear palsy (PSP) is a 4R-tauopathy predominated by subcortical pathology in neurons, astrocytes, and oligodendroglia associated with various clinical phenotypes. In the present international study, we addressed question of whether or not sequential distribution patterns can be recognized for PSP pathology. We evaluated heat maps neuronal, astroglial, oligodendroglial tau pathologies their combinations different subtypes postmortem brains. used conditional probability...
The microtubule-binding protein, tau, is the major component of neurofibrillary inclusions characteristic Alzheimer's disease and related neurodegenerative tauopathies. When tau fibrillizes, it undergoes abnormal post-translational modifications resulting in decreased solubility altered microtubule-stabilizing properties. Recently, we reported that acetylation at lysine residue 280 a novel, pathological modification. Here, performed detailed immunohistochemistry to further examine...
Neuronal and axonal destruction are hallmarks of neurodegenerative diseases, but it is difficult to estimate the extent progress damage in disease process.To investigate cerebrospinal fluid (CSF) levels neurofilament light (NFL) protein, a marker neuroaxonal degeneration, control participants patients with dementia, motor neuron disease, parkinsonian disorders (determined by clinical criteria autopsy), determine its association longitudinal cognitive decline.In this case-control study, we...
ABSTRACT Background Neurofilament light chain protein (NfL) is a promising biomarker of neurodegeneration. Objectives To determine whether plasma and CSF NfL (1) associate with motor or cognitive status in Parkinson's disease (PD) (2) predict future decline PD. Methods Six hundred fifteen participants neurodegenerative diseases, including 152 PD 200 healthy control participants, provided and/or cerebrospinal fluid (CSF) sample. Diagnostic groups were compared using the Kruskal−Wallis rank...
Abstract Tau pathology is the main driver of neuronal dysfunction in 4-repeat tauopathies, including cortico-basal degeneration and progressive supranuclear palsy. assumed to spread prion-like across connected neurons, but mechanisms tau propagation are largely elusive characterized not only by also astroglial oligodendroglial accumulation. Here, we assess whether connectivity associated with 4R-tau deposition patterns combining resting-state fMRI connectomics both 2 nd generation 18...
Pathologies that are causative for neurodegenerative disease (ND) also frequently present in unimpaired, older individuals. In this retrospective study of 1647 autopsied individuals, we report the incidence 10 pathologies across ND and normal ageing attempt to clarify which pathological combinations disease-associated ageing-related. Eight clinically defined groups were examined including unimpaired individuals those with clinical Alzheimer's disease, mixed dementia, amyotrophic lateral...