Richard J. Perrin
A5010912426- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Functional Brain Connectivity Studies
- Bioinformatics and Genomic Networks
- Parkinson's Disease Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced Neuroimaging Techniques and Applications
- Health, Environment, Cognitive Aging
- Metabolomics and Mass Spectrometry Studies
- Genetic Associations and Epidemiology
- Neurological Disease Mechanisms and Treatments
- Neurological diseases and metabolism
- Prion Diseases and Protein Misfolding
- Tryptophan and brain disorders
- Down syndrome and intellectual disability research
- Frailty in Older Adults
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Advanced Proteomics Techniques and Applications
- Intracerebral and Subarachnoid Hemorrhage Research
- Neurological disorders and treatments
- S100 Proteins and Annexins
- Single-cell and spatial transcriptomics
- Nuclear Receptors and Signaling
- Meningioma and schwannoma management
- Chronic Disease Management Strategies
Washington University in St. Louis
2016-2025
Alzheimer’s Disease Neuroimaging Initiative
2022-2025
Hope Center for Neurological Disorders
2013-2024
Mallinckrodt (United States)
2007-2024
University of Ulsan
2024
Asan Medical Center
2024
Dankook University
2024
Ulsan College
2024
Hospital for Sick Children
2024
California University of Pennsylvania
2024
α-Synuclein has been centrally implicated in neurodegenerative disease, and a normal function developmental synaptic plasticity suggested by studies songbirds. A variety of observations suggest the protein partitions between membrane cytosol, behavior apparently conferred conserved structural similarity to exchangeable apolipoproteins. Here we show that capacity bind lipids is broadly distributed across exons 3, 4, 5 (encoding residues 1–102). Binding phosphatidylserine-containing vesicles...
<h3>Objectives:</h3> While plasma biomarkers have been proposed to aid in the clinical diagnosis of Alzheimer disease (AD), few validated independent patient cohorts. Here we aim determine associated with AD 2 cohorts and validate findings multicenter Alzheimer9s Disease Neuroimaging Initiative (ADNI). <h3>Methods:</h3> Using a targeted proteomic approach, measured levels 190 proteins peptides 600 participants from centers (University Pennsylvania, Philadelphia; Washington University, St....
Macrophages are important players in the maintenance of tissue homeostasis1. Perivascular and leptomeningeal macrophages reside near central nervous system (CNS) parenchyma2, their role CNS physiology has not been sufficiently well studied. Given continuous interaction with cerebrospinal fluid (CSF) strategic positioning, we refer to these cells collectively as parenchymal border (PBMs). Here demonstrate that PBMs regulate CSF flow dynamics. We identify a subpopulation express high levels...
Alzheimer’s disease (AD) is the most common form of dementia. This neurodegenerative disorder associated with neuronal death and gliosis heavily impacting cerebral cortex. AD has a substantial but heterogeneous genetic component, presenting both Mendelian complex architectures. Using bulk RNA-seq from parietal lobes deconvolution methods, we previously reported that brains exhibiting different architecture exhibit cellular proportions. Here, sought to directly investigate brain changes in...
Abstract Alzheimer’s disease (AD) pathology develops many years before the onset of cognitive symptoms. Two pathological processes—aggregation amyloid-β (Aβ) peptide into plaques and microtubule protein tau neurofibrillary tangles (NFTs)—are hallmarks disease. However, other brain processes are thought to be key mediators Aβ plaque NFT pathology. How these additional pathologies evolve over course is currently unknown. Here we show that proteomic measurements in autosomal dominant AD...
The gap between chronological age (CA) and biological brain age, as estimated from magnetic resonance images (MRIs), reflects how individual patterns of neuroanatomic aging deviate their typical trajectories. MRI-derived (BA) estimates are often obtained using deep learning models that may perform relatively poorly on new data or lack interpretability. This study introduces a convolutional neural network (CNN) to estimate BA after training the MRIs 4,681 cognitively normal (CN) participants...
Genetic studies of Alzheimer disease (AD) have prioritized variants in genes related to the amyloid cascade, lipid metabolism, and neuroimmune modulation. However, cell-specific effect these is not fully understood. Here, we perform single-nucleus RNA-sequencing (snRNA-seq) on nearly 300,000 nuclei from parietal cortex AD autosomal dominant (APP PSEN1) risk-modifying variant (APOE, TREM2 MS4A) carriers. Within individual cell types, capture commonly dysregulated across groups. specific...
Proteomic studies for Alzheimer’s disease (AD) are instrumental in identifying AD pathways but often focus on single tissues and sporadic cases. Here, we present a proteomic study analyzing 1305 proteins brain tissue, cerebrospinal fluid (CSF), plasma from patients with AD, TREM2 risk variant carriers, autosomal dominant (ADAD), healthy individuals. We identified 8 brain, 40 CSF, 9 that were altered individuals replicated these findings several external datasets. signature differentiated...
Abstract The defining feature of Parkinson disease (PD) and Lewy body dementia (LBD) is the accumulation alpha-synuclein (Asyn) fibrils in bodies neurites. Here we develop validate a method to amplify Asyn extracted from LBD postmortem tissue samples use solid state nuclear magnetic resonance (SSNMR) studies determine atomic resolution structure. Amplified comprise mixture single protofilament two with very low twist. fold highly similar determined by recent cryo-electron microscopy study...
Abstract Triggering receptor expressed on myeloid cells 2 (TREM2) plays a critical role in microglial activation, survival, and apoptosis, as well Alzheimer’s disease (AD) pathogenesis. We previously reported the MS4A locus key modulator for soluble TREM2 (sTREM2) cerebrospinal fluid (CSF). To identify additional novel genetic modifiers of sTREM2, we performed largest genome-wide association study (GWAS) identified four loci CSF sTREM2 3,350 individuals European ancestry. Through...
Abstract INTRODUCTION Alzheimer's disease (AD) pathology is defined by β‐amyloid (Aβ) plaques and neurofibrillary tau, but Lewy bodies (LBs; 𝛼‐synuclein aggregates) are a common co‐pathology for which effective biomarkers needed. METHODS A validated α‐synuclein Seed Amplification Assay (SAA) was used on recent cerebrospinal fluid (CSF) samples from 1638 Disease Neuroimaging Initiative (ADNI) participants, 78 with LB‐pathology confirmation at autopsy. We compared SAA outcomes neuropathology,...
Importance The ability to predict the onset of mild cognitive impairment (MCI) and Alzheimer dementia (AD) could allow older adults clinicians make informed decisions about care. Objective To assess whether age at MCI AD can be predicted using a statistical modeling approach. Design, Setting, Participants This prognostic study used data from 2 aging cohort studies—the Australian Imaging, Biomarker Lifestyle (AIBL) Alzheimer’s Disease Neuroimaging Initiative (ADNI)—for model development...
Abstract We present a comprehensive global analysis of genetic variants associated with autosomal-dominant Alzheimer's disease (ADAD). A total 550 in the APP, PSEN1, and PSEN2 genes were identified, which 279 classified as pathogenic or likely based on ACMG-AMP criteria, utilizing data from Dominantly Inherited Alzheimer Network (DIAN), literature, public databases. Symptomatic age at onset (AAO) was estimated for 227 these variants, allowing detailed characterization their frequency,...
Detergent-stable multimers of alpha-synuclein have been found specifically in the brains patients with Parkinson's disease and other neurodegenerative diseases. Here we show that recombinant forms vitro upon exposure to vesicles containing certain polyunsaturated fatty acid (PUFA) acyl groups, including arachidonoyl docosahexaenoyl. This process occurs at physiological concentrations much faster than aqueous solution. PUFA-induced aggregation involves physical association vesicle surface via...