A5025691323- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Memory and Neural Mechanisms
- Prion Diseases and Protein Misfolding
- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Monoclonal and Polyclonal Antibodies Research
- Neural dynamics and brain function
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Olfactory and Sensory Function Studies
- Advanced Biosensing Techniques and Applications
- Neurological diseases and metabolism
- Nicotinic Acetylcholine Receptors Study
- Photoreceptor and optogenetics research
- Extracellular vesicles in disease
- Protein purification and stability
- Click Chemistry and Applications
The University of Texas at Austin
2016-2024
Harvard University
2014-2018
Brigham and Women's Hospital
2013-2018
University College Dublin
2011-2013
Synthetic amyloid-β protein (Aβ) oligomers bind with high affinity to cellular prion (PrP C ), but the role of this interaction in mediating disruption synaptic plasticity by such soluble Aβ vitro is controversial. Here we report that intracerebroventricular injection Aβ-containing aqueous extracts Alzheimer's disease (AD) brain robustly inhibits long-term potentiation (LTP) without significantly affecting baseline excitatory transmission rat hippocampus vivo . Moreover, LTP was abrogated...
Exosomes, small extracellular vesicles of endosomal origin, have been suggested to be involved in both the metabolism and aggregation Alzheimer's disease (AD)-associated amyloid β-protein (Aβ). Despite their ubiquitous presence inclusion components which can potentially interact with Aβ, role exosomes regulating synaptic dysfunction induced by Aβ has not explored. We here provide vivo evidence that derived from N2a cells or human cerebrospinal fluid abrogate synaptic-plasticity-disrupting...
Abstract NMDA-type glutamate receptors (NMDARs) are currently regarded as paramount in the potent and selective disruption of synaptic plasticity by Alzheimer’s disease amyloid β-protein (Aβ). Non-NMDAR mechanisms remain relatively unexplored. Here we describe how Aβ facilitates NMDAR-independent long-term depression transmission hippocampus vivo . Synthetic soluble extracts brain usurp endogenous acetylcholine muscarinic receptor-dependent depression, to enable that required metabotropic...
ABSTRACT Alzheimer's disease (AD) is an irreversible and highly progressive neurodegenerative disease. Clinically, patients with AD display impairments in episodic spatial memory. However, the underlying neuronal dysfunctions that result these remain poorly understood. The hippocampus crucial for memory, thus we tested hypothesis abnormal representations of space contribute to memory deficits AD. To test this hypothesis, recorded spikes from place cells hippocampal subfield CA1, together...
Intracellular neurofibrillary tangles (NFTs) composed of tau protein are a neuropathological hallmark several neurodegenerative diseases, the most common which is Alzheimer's disease (AD). For some time NFTs were considered primary cause synaptic dysfunction and neuronal death, however, more recent evidence suggests that soluble aggregates key drivers disease. Here we investigated effect different species on plasticity in male rat hippocampus vivo . Intracerebroventricular injection formed...
Alzheimer's disease (AD) is associated with pathological assembly states of amyloid-β protein (Aβ). Aβ-related synaptotoxicity can be blocked by anti-prion (PrP) antibodies, potentially allowing therapeutic targeting this aspect AD neuropathogenesis. Here, we show that intravascular administration a high-affinity humanized anti-PrP antibody to rats prevent the plasticity-disrupting effects induced exposure soluble brain extract. These results provide an in vivo proof principle for such strategy.
Abstract Introduction Much knowledge about amyloid β (Aβ) aggregation and toxicity has been acquired using synthetic peptides mouse models, whereas less is known soluble Aβ in human brain. Methods We analyzed aqueous extracts from multiple AD brains an array of techniques. Results Brains can contain at least four different assembly forms including: (i) monomers, (ii) a ∼7kDa species, larger species (iii) ∼30‐150 kDa, (iv) >160 kDa. High molecular weight are by far the most prevalent...
Dysregulation of glutamate homeostasis in the interstitial fluid brain is strongly implicated causing synaptic dysfunction many neurological and psychiatric illnesses. In case Alzheimer's disease (AD), amyloid β (Aβ)-mediated disruption plasticity memory can be alleviated by interventions that directly remove or block certain receptors. An alternative strategy to facilitate removal excess from nervous system activating peripheral clearance systems. One such blood-based system, oxaloacetate...
Many endogenous factors influence the time course and extent of detrimental effects amyloid β-protein (Aβ) on synaptic function. Here, we assessed impact varying glutamatergic cholinergic transmission by pharmacological means disruption plasticity at hippocampal CA3-to-CA1 synapses in anaesthetized rat. NMDA receptors (NMDARs) are considered critical mediating Aβ-induced inhibition long-term potentiation (LTP). However, intracerebroventricular injection Aβ 1–42 inhibited not only...
Alzheimer's disease (AD) and familial Danish dementia (FDD) are degenerative neurological diseases characterized by amyloid pathology. Normal human sera contain IgG antibodies that specifically bind diverse preamyloid proteins have shown therapeutic potential in vitro vivo . We cloned one of these antibodies, 3H3, from memory B cells a healthy individual using hybridoma method. 3H3 is an affinity-matured binds pan-amyloid epitope, recognizing both Aβ λ Ig light chain (LC) amyloids, which...
CA1 place cells become more anticipatory with experience, an effect thought to be caused by NMDA receptor-dependent plasticity in the CA3-CA1 network. Theta (~5-12 Hz), slow gamma (~25-50 and fast (~50-100 Hz) rhythms are route spatial information hippocampal formation coordinate cell ensembles. Yet, it is unknown whether these exhibit experience-dependent changes concurrent those observed cells. Slow indicate inputs from CA3 CA1, such strengthened experience. Thus, we hypothesized that...
Abstract Hippocampal region CA2 is essential for social memory processing. Interaction with stimuli induces changes in place cell firing during active exploration and sharp wave-ripples rest following a interaction. However, it unknown whether these patterns are caused by integration of multimodal or specific sensory modality associated Rodents rely heavily on chemosensory cues the form olfactory signals recognition processes. To determine extent to which contribute responses stimuli, we...
Humanized anti-Abeta murine monoclonal IgGs (mAbs) generated against linear or conformational epitopes are investigational therapeutics that being developed for Alzheimer's disease (AD). Such antibodies may have pan-Abeta conformer reactivity preferential binding to a specific peptide (aggregates monomer) due unique exposed surface(s) and/or avidity effects (bivalent binding). To advance understanding on the Abeta of clinically tested mAbs, we used battery solid- and solution-phase assays...
Previously, we showed that water-soluble extracts from Alzheimer's disease (AD) human brain contain aggregates of amyloid-beta protein (Aβ) and inhibit long-term potentiation (LTP), a form synaptic plasticity believed to be necessary for successful memory function (Barry et al., 2011; Freir 2011). Here, tried evaluate the effects insoluble, plaque core-containing preparations AD brain. In vivo experiments were carried out on urethane-anaesthetized rats under approval Trinity College Dublin's...