A5042907016- Alzheimer's disease research and treatments
- Parkinson's Disease Mechanisms and Treatments
- Nuclear Receptors and Signaling
- Advanced MRI Techniques and Applications
- Advanced Neuroimaging Techniques and Applications
- Neuroinflammation and Neurodegeneration Mechanisms
- Cholinesterase and Neurodegenerative Diseases
- Neurological disorders and treatments
- S100 Proteins and Annexins
- MRI in cancer diagnosis
- Amyotrophic Lateral Sclerosis Research
- Diet and metabolism studies
- Computational Drug Discovery Methods
- Tryptophan and brain disorders
- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Neurological and metabolic disorders
- Prion Diseases and Protein Misfolding
- Biotin and Related Studies
- Dementia and Cognitive Impairment Research
- Cholesterol and Lipid Metabolism
- RNA regulation and disease
- Characterization and Applications of Magnetic Nanoparticles
- Mitochondrial Function and Pathology
- Nerve injury and regeneration
Psychogenics (United States)
2016-2025
QPS (Austria)
2012-2018
Brigham and Women's Hospital
2010
Harvard University
2010
University of Helsinki
2010
MaineGeneral Medical Center
2010
Massachusetts General Hospital
2010
CNS Research (United States)
2008-2009
Effective therapies are urgently needed to safely target TDP-43 pathology as it is closely associated with the onset and development of devastating diseases such frontotemporal lobar degeneration (FTLD-TDP) amyotrophic lateral sclerosis (ALS). In addition, present a co-pathology in other neurodegenerative Alzheimer's disease Parkinson's disease. Our approach develop TDP-43-specific immunotherapy that exploits Fc gamma-mediated removal mechanisms limit neuronal damage while maintaining...
A hallmark of Alzheimer's disease is the presence senile plaques in human brain primarily containing amyloid peptides Aβ42 and Aβ40. Many drug discovery efforts have focused on decreasing production through γ-secretase inhibition. However, identification inhibitors has also uncovered mechanism-based side effects. One approach to circumvent these effects been modulation shift Aβ favor shorter, less amyloidogenic than Aβ42, without affecting overall cleavage efficiency enzyme. This approach,...
Cerebral accumulation of amyloid-β (Aβ) is characteristic Alzheimer disease and amyloid precursor protein (APP) transgenic mice. Here, we assessed the efficacy CI-1011, an inhibitor acyl-coenzyme A:cholesterol acyltransferase, which suitable for clinical use, in reducing pathology both young (6.5 months old) aged (16 human APP Treatment animals with CI-1011 decreased plaque load cortex hippocampus reduced levels insoluble Aβ40 Aβ42 C-terminal fragments brain extracts. In mice, specifically...
Elucidating the age-dependent alterations in transgenic (Tg) mice overexpressing amyloid-β protein precursor (AβPP) is important for understanding pathogenesis of Alzheimer's disease (AD) and designing experimental therapies. Cross-studies have previously characterized some time-dependent behavioral pathological AβPP Tg mice, however, a more comprehensive longitudinal study needed to fully examine progressive nature deficits these mice. In order better understand age- gender-dependent...
Abstract Background Progressive accumulation of α-synuclein (α-Syn) protein in different brain regions is a hallmark synucleinopathic diseases, such as Parkinson’s disease, dementia with Lewy bodies and multiple system atrophy. α-Syn transgenic mouse models have been developed to investigate the effects on behavioral deficits neuropathology. However, onset progression pathology mice not fully characterized. For this purpose we investigated time course neuropathology PDGF-β human wild type...
The cis-conformer of tau phosphorylated at threonine-231 (cis-pT231 tau) is hypothesized to contribute tauopathies. PNT001 a humanized, monoclonal antibody that recognizes cis-pT231 tau. was characterized assess clinical development readiness.Affinity and selectivity were assessed by surface plasmon resonance enzyme-linked immunosorbent assay. Immunohistochemistry (IHC) performed with brain sections from human tauopathy patients controls. Real-time quaking-induced conversion (RT-QuIC) used...
Abstract Aim Astrocytes respond to stressors by acquiring a reactive state characterized changes in their morphology and function. Molecules underlying astrogliosis, however, remain largely unknown. Given that several studies observed increase the Amyloid Precursor Protein (APP) astrocytes, we here test whether APP plays role astrogliosis. Methods We investigated instigates astroglios examining vitro vivo function of naive APP‐deficient astrocytes response well‐established stressors. Results...
The Alzheimer's disease (AD)-affected brain is known to be deficient in the utilization of glucose, its main energy substrate, and systemic diabetes a significant risk factor for AD. In course biochemical molecular investigations into this puzzling relationship, it has been shown that resistance insulin action prominent feature early stages AD brain, thereby contributing an failure state decline synaptic function. one AD-like cellular model, we found β-amyloid (Aβ) accumulation inhibited...
Abstract INTRODUCTION Amyloid precursor protein (APP) undergoes striking changes following traumatic brain injury (TBI). Considering its role in the control of gene expression, we investigated whether APP regulates transcription and translation TBI. METHODS We assessed morphology ( n = 4–9 mice/group), transcriptome 3 proteome behavior 17–27 mice/group) wild‐type (WT) knock‐out (KO) mice either untreated or 10‐weeks RESULTS After TBI, WT displayed transcriptional programs consistent with...
Abstract Diffusion kurtosis imaging ( DKI ) by measuring non‐Gaussian diffusion allows an accurate estimation of the distribution water molecule displacement and may correctly characterize microstructural brain changes caused neurodegeneration. The aim this study was to evaluate ability detect induced α‐synuclein (α‐syn) accumulation in α‐syn over‐expressing transgenic mice TNWT ‐61) both gray matter GM white WM using region interest ROI tract‐based spatial statistics analyses, respectively,...
It is intriguing that a rare, inherited lysosomal storage disorder Niemann-Pick type C (NPC) shares similarities with Alzheimer's disease (AD). We have previously reported an enhanced processing of β-amyloid precursor protein (APP) by β-secretase (BACE1), key enzyme in the pathogenesis AD, NPC1-null cells. In this work, we characterized regional and temporal expression recently identified BACE1 substrates seizure 6 (Sez6) 6-like (Sez6L), APP, NPC1-/- (NPC1) NPC1+/+ (wt) mouse brains....
Beyond cognitive decline, Alzheimer's disease (AD) is characterized by numerous neuropathological changes in the brain. Although animal models generally do not fully reflect broad spectrum of disease-specific alterations, APPSL mouse model well known to display early plaque formation and exhibit spatial learning memory deficits. However, important features, such as neuroinflammation lipid peroxidation, their progression over age, have yet been described this AD model. Hippocampal neocortical...
Accumulation of amyloid-β (Aβ) cascade aggregates is considered a hallmark Alzheimer's disease (AD). Current dogma holds that the appearance Aβ oligomers and larger occur many years prior to plaque formation associated with advanced irreparable neurocognitive decline characteristic AD. This premise impetus identify these precursor structures development. The Pronucleon™ technology platform comprised novel series engineered peptides provide unique readout when beta-rich fiber oligomeric Aβ....
The formation and accumulation of toxic amyloid-β peptides (Aβ) in the brain may drive pathogenesis Alzheimer's disease. Accordingly, disease-modifying therapies for disease related disorders could result from treatments regula
Abstract Mitochondrial dysfunction is an early feature of Alzheimer's disease ( AD ) and may play important role in the pathogenesis disease. It has been shown that amyloid beta peptide (Aβ) precursor protein APP interact with mitochondria contributing to mitochondrial . Prevention abnormal targeting can protect normal function, increase neuronal survival at end, ameliorate symptoms other neurodegenerative disorders. First steps import are coordinated by molecular chaperones Hsp70 Hsp90 bind...
This study was performed to explore the feasibility of tracing nanoparticles for drug transport in healthy rat brain with a clinical MRI scanner. Phantom studies were assess R1 ( = 1/T1) relaxivity different magnetically labeled nanoparticle (MLNP) formulations that based on biodegradable human serum albumin and magnetite size. In vivo measurements 26 rats done at 3T effect dynamics MLNP uptake body. brain, MLNPs induced T1 changes quantitatively assessed by relaxation time mapping compared...
Experimental studies in flies, mice, and humans suggest a significant role of impaired axonal transport the pathogenesis Alzheimer's disease (AD). The mechanisms underlying these impairments transport, however, remain poorly understood. Here we report that Swedish familial AD mutation causes standstill Amyloid Precursor Protein (APP) axons at expense its reduced anterograde transport. reflects perturbed directionality APP, which spends significantly more time traveling retrograde direction....
<b><i>Background:</i></b> β-Synuclein (β-Syn) is a member of the highly homologous synuclein protein family. The most prominent family member, α-synuclein (α-Syn), abnormally accumulates in so-called Lewy bodies, one major pathological hallmarks α-synucleinopathies. Notably, parts peptide backbone, called nonamyloid component, are also found amyloid plaques. However, β-Syn seems to have beneficial effects by reducing α-Syn aggregation, and antiaggregatory activity has...
Aggregates of hyperphosphorylated Tau protein are characteristics tauopathies and many other neurodegenerative diseases (ND). The physiological role tau in the central nervous systems (CNS) is assembly stability microtubuli, a process that requires homeostatic balance between kinase phosphorylation phosphatase dephosphorylation. Hyperphosphorylated has been shown to dissociate from resulting breakdown axonal flow, impaired neuronal viability, function. Since presents promising target for...