Alzheimer's Disease R&D Review
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Structural tract alterations predict downstream tau accumulation in amyloid-positive older individuals

Structural tract alterations predict downstream tau accumulation in amyloid-positive older individuals | Alzheimer's Disease R&D Review | Scoop.it

Our results provide in vivo evidence that higher amyloid pathology strengthens the association between HCB diffusivity and tau accumulation in the downstream posterior cingulate cortex and facilitates memory decline. This confirms amyloid’s crucial role in potentiating neural vulnerability and memory decline marking the onset of preclinical Alzheimer’s disease.

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Alzheimer's Disease R&D Review
A review of the Solanezumab (Lilly), Gantenerumab (Roche) the 2  beta amyloid monoclonal antibodies  in Phase III trials and other potential targets is provided. The failure of Bapineuzumab in Phase III trials in 2012 puta question mark on the validity of beta amyloid hypothesis. Bapineuzumab is a fully humanized monoclonal antibody which targets beta amyloid protein involved in Alzheimer's Disease. There are 26 million patients in the world, half in Asia and the rest in N America/Europe with AD.
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Created public version #237 of the knol: "Bapineuzumab (Pfizer, J&J, Elan) Review"

Created public version #237 of the knol: "Bapineuzumab (Pfizer, J&J, Elan) Review" | Alzheimer's Disease R&D Review | Scoop.it
Krishan Maggon published version 237 of a knol titled: "Bapineuzumab (Pfizer, J&J, Elan) Review"...
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Functioning Human Neural Networks Grown in 3D from Stem Cells

Functioning Human Neural Networks Grown in 3D from Stem Cells | Alzheimer's Disease R&D Review | Scoop.it
Functioning Human Neural Networks Grown in 3D from Stem Cells Reporter: Irina Robu, PhD   Researchers at Tuffs University developed three-dimensional human tissue model that mimics structural and functional features of the brain and were able to demonstrate sustained neural activity over several...
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Analysis of multiply charged monomers and dimers of human islet amyloid polypeptide by collision-induced dissociation with electrospray ionization mass spectrometry - ScienceDirect

Analysis of multiply charged monomers and dimers of human islet amyloid polypeptide by collision-induced dissociation with electrospray ionization mass spectrometry - ScienceDirect | Alzheimer's Disease R&D Review | Scoop.it
Highlights

Multiply charged monomers and dimers of hIAPP were investigated through CID-MS/MS.


hIAPP monomers adopt different structures depending on the parent ion charge state.


hIAPP 1-15 are proposed as an interaction area in dimers in low energy CID conditions.
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Defective Glial Cells Can Push Neurons Toward Parkinson's Disease

Defective Glial Cells Can Push Neurons Toward Parkinson's Disease | Alzheimer's Disease R&D Review | Scoop.it
A new study reveals a defective version of astrocytes may be linked to the build up of alpha synuclein and could spur Parkinson's disease. The findings show the important role glial cells play in Parkinson's and offers insights into new targets for therapies to fight the neurodegenerative disease.
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Neuro–Immune Cell Units: A New Paradigm in Physiology | Annual Review of Immunology

Neuro–Immune Cell Units: A New Paradigm in Physiology | Annual Review of Immunology | Alzheimer's Disease R&D Review | Scoop.it
Abstract
The interplay between the immune and nervous systems has been acknowledged in the past, but only more recent studies have started to unravel the cellular and molecular players of such interactions. Mounting evidence indicates that environmental signals are sensed by discrete neuro–immune cell units (NICUs), which represent defined anatomical locations in which immune and neuronal cells colocalize and functionally interact to steer tissue physiology and protection. These units have now been described in multiple tissues throughout the body, including lymphoid organs, adipose tissue, and mucosal barriers. As such, NICUs are emerging as important orchestrators of multiple physiological processes, including hematopoiesis, organogenesis, inflammation, tissue repair, and thermogenesis. In this review we focus on the impact of NICUs in tissue physiology and how this fast-evolving field is driving a paradigm shift in our understanding of immunoregulation and organismal physiology.

Expected final online publication date for the Annual Review of Immunology Volume 37 is April 26, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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Scientists Identify The Physical Source of Anxiety in The Brain

Scientists Identify The Physical Source of Anxiety in The Brain | Alzheimer's Disease R&D Review | Scoop.it
A 2018 study investigating the neurological basis of anxiety in the brain has identified 'anxiety cells' located in the hippocampus – which not only regulate anxious behaviour but can be controlled by a beam of light.

The findings, so far demonstrated in experiments with lab mice, could offer a ray of hope for the millions of people worldwide who experience anxiety disorders (including almost one in five adults in the US), by leading to new drugs that silence these anxiety-controlling neurons.
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An in-depth structural view of a GABAA brain receptor

An in-depth structural view of a GABAA brain receptor | Alzheimer's Disease R&D Review | Scoop.it
Detailed structures of a GABA receptor bound to different ligands.
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Structural basis of Notch recognition by human γ-secretase

Structural basis of Notch recognition by human γ-secretase | Alzheimer's Disease R&D Review | Scoop.it
The cryo-electron microscopy structure of human γ-secretase in complex with its substrate Notch reveals pronounced structural rearrangements compared to the apo enzyme, including formation of a β-sheet involving residues from both enzyme and substrate.

 

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Human Blood Cells Directly Reprogrammed Into Neural Stem Cells

Human Blood Cells Directly Reprogrammed Into Neural Stem Cells | Alzheimer's Disease R&D Review | Scoop.it
For the first time, human blood cells have been directly reprogrammed into a previously unknown type of neural stem cell, report scientists from the German Cancer Research Center (DKFZ) and the stem cell institute HI-STEM in Heidelberg.
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A Comprehensive Analysis of Protocols for Deriving Dopaminergic Neurons from Human Pluripotent Stem Cells - Marton - - STEM CELLS Translational Medicine - Wiley Online Library

STEM CELLS Translational Medicine works to advance the clinical utilization of stem cell molecular and cellular biology. By bridging stem cell research and helping speed translations of emerging lab discoveries into clinical trials, STEM CELLS Translational Medicine will help move applications of...
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Epigenome-wide study uncovers large-scale changes in histone acetylation driven by tau pathology in aging and Alzheimer’s human brains

Epigenome-wide study uncovers large-scale changes in histone acetylation driven by tau pathology in aging and Alzheimer’s human brains | Alzheimer's Disease R&D Review | Scoop.it
Accumulation of tau and amyloid-β are two pathologic hallmarks of Alzheimer’s disease. We conducted an epigenome-wide association study using the histone 3 lysine 9 acetylation (H3K9ac) mark in 669 aged human prefrontal cortices; in contrast with amyloid-β, tau protein burden had a broad effect on the epigenome, affecting 5,990 of 26,384 H3K9ac domains. Tau-related alterations aggregated in large genomic segments reflecting spatial chromatin organization, and the magnitude of these effects correlated with the segment’s nuclear lamina association. Functional relevance of these chromatin changes was demonstrated by (1) consistent transcriptional changes in three independent datasets and (2) similar findings in two mouse models of Alzheimer’s disease. Finally, we found that tau overexpression in induced pluripotent stem cell-derived neurons altered chromatin structure and that these effects could be blocked by a small molecule predicted to reverse the tau effect. Thus, we report broad tau-driven chromatin rearrangements in the aging human brain that may be reversible with heat-shock protein 90 (Hsp90) inhibitors.
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Cracking the Function of Layers in the Sensory Cortex

Understanding how cortical activity generates sensory perceptions requires a detailed dissection of the function of cortical layers. Despite our relatively extensive knowledge of their anatomy and wiring, we have a limited grasp of what each layer contributes to cortical computation. We need to develop a theory of cortical function that is rooted solidly in each layer’s component cell types and fine circuit architecture and produces predictions that can be validated by specific perturbations. Here we briefly review the progress toward such a theory and suggest an experimental road map toward this goal. We discuss new methods for the all-optical interrogation of cortical layers, for correlating in vivo function with precise identification of transcriptional cell type, and for mapping local and long-range activity in vivo with synaptic resolution. The new technologies that can crack the function of cortical layers are finally on the immediate horizon.
Keywords
cortex
cortical layers
neural codes
neurotechnology
optogenetics
neural computation
neural circuits
inhibitory circuits
cortical microcircuits
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Mapping Symptoms to Brain Networks with the Human Connectome | NEJM

Mapping Symptoms to Brain Networks with the Human Connectome | NEJM | Alzheimer's Disease R&D Review | Scoop.it
Complex neurologic and psychiatric syndromes cannot be understood on the basis of focal brain lesions. Functional neuroimaging, maps of interrelated regions called the connectome, and the combination of lesion analysis with networks of the connectome offer a new way to understand neurologic function and disease.
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Reduced non–rapid eye movement sleep is associated with tau pathology in early Alzheimer’s disease

Reduced non–rapid eye movement sleep is associated with tau pathology in early Alzheimer’s disease | Alzheimer's Disease R&D Review | Scoop.it
In patients with Alzheimer’s disease (AD), amyloid-β (Aβ) plaques and tau protein tangles accumulate in the brain long before the appearance of clinical symptoms. Early intervention is critical for slowing neurodegeneration and disease progression. Therefore, reliable markers of early AD are needed. Lucey et al. analyzed sleep patterns in aging cognitively normal subjects and showed that non–rapid eye movement (NREM) sleep negatively correlated with tau pathology and Aβ deposition in several brain areas. The results show that alterations in NREM sleep may be an early indicator of AD pathology and suggest that noninvasive sleep analysis might be useful for monitoring patients at risk for developing AD.

In Alzheimer’s disease (AD), deposition of insoluble amyloid-β (Aβ) is followed by intracellular aggregation of tau in the neocortex and subsequent neuronal cell loss, synaptic loss, brain atrophy, and cognitive impairment. By the time even the earliest clinical symptoms are detectable, Aβ accumulation is close to reaching its peak and neocortical tau pathology is frequently already present. The period in which AD pathology is accumulating in the absence of cognitive symptoms represents a clinically relevant time window for therapeutic intervention. Sleep is increasingly recognized as a potential marker for AD pathology and future risk of cognitive impairment. Previous studies in animal models and humans have associated decreased non–rapid eye movement (NREM) sleep slow wave activity (SWA) with Aβ deposition. In this study, we analyzed cognitive performance, brain imaging, and cerebrospinal fluid (CSF) AD biomarkers in participants enrolled in longitudinal studies of aging. In addition, we monitored their sleep using a single-channel electroencephalography (EEG) device worn on the forehead. After adjusting for multiple covariates such as age and sex, we found that NREM SWA showed an inverse relationship with AD pathology, particularly tauopathy, and that this association was most evident at the lowest frequencies of NREM SWA. Given that our study participants were predominantly cognitively normal, this suggested that changes in NREM SWA, especially at 1 to 2 Hz, might be able to discriminate tau pathology and cognitive impairment either before or at the earliest stages of symptomatic AD.
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Gastrointestinal Dysfunctions Are Associated with IL-10 Variants in Parkinson’s Disease

Gastrointestinal Dysfunctions Are Associated with IL-10 Variants in Parkinson’s Disease | Alzheimer's Disease R&D Review | Scoop.it
Parkinson’s Disease is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies related to the epidemiology, etiology, pathogenesis, genetics, cellular, molecular and neurophysiology, as well as the diagnosis and treatment of Parkinson’s...
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Defective Glial Cells Can Push Neurons Toward Parkinson's Disease

Defective Glial Cells Can Push Neurons Toward Parkinson's Disease | Alzheimer's Disease R&D Review | Scoop.it
A new study reveals a defective version of astrocytes may be linked to the build up of alpha synuclein and could spur Parkinson's disease. The findings show the important role glial cells play in Parkinson's and offers insights into new targets for therapies to fight the neurodegenerative disease.
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What Happens with the Circuit in Alzheimer's Disease in Mice and Humans? | Annual Review of Neuroscience

What Happens with the Circuit in Alzheimer's Disease in Mice and Humans? | Annual Review of Neuroscience | Alzheimer's Disease R&D Review | Scoop.it
Abstract
A major mystery of many types of neurological and psychiatric disorders, such as Alzheimer's disease (AD), remains the underlying, disease-specific neuronal damage. Because of the strong interconnectivity of neurons in the brain, neuronal dysfunction necessarily disrupts neuronal circuits. In this article, we review evidence for the disruption of large-scale networks from imaging studies of humans and relate it to studies of cellular dysfunction in mouse models of AD. The emerging picture is that some forms of early network dysfunctions can be explained by excessively increased levels of neuronal activity. The notion of such neuronal hyperactivity receives strong support from in vivo and in vitro cellular imaging and electrophysiological recordings in the mouse, which provide mechanistic insights underlying the change in neuronal excitability. Overall, some key aspects of AD-related neuronal dysfunctions in humans and mice are strikingly similar and support the continuation of such a translational strategy.

Keywords
default mode network, hippocampus, slow-wave oscillations, memory consolidation, hyperactivity, imaging
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Exercise-induced hormone may protect against Alzheimer’s and dementia

Exercise-induced hormone may protect against Alzheimer’s and dementia | Alzheimer's Disease R&D Review | Scoop.it
A new study has revealed a compelling association between a hormone released during exercise and the prevention of neurodegeneration seen in conditions such as Alzheimer's disease. The research in mice suggests the exercise-induced hormone irisin may improve brain plasticity and memory, helping explain how exercise confers beneficial effects on brain health.
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Stem cell study reveals clues into early development of autism spectrum disorder –

Stem cell study reveals clues into early development of autism spectrum disorder – | Alzheimer's Disease R&D Review | Scoop.it
Autism spectrum disorder (ASD) is a relatively common developmental disorder of communication and behavior that affects about 1 in 59 children in the US, according to the Centers for Disease Control and Prevention.
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Promising new Alzheimer’s treatment unexpectedly found in old antibiotic

Promising new Alzheimer’s treatment unexpectedly found in old antibiotic | Alzheimer's Disease R&D Review | Scoop.it
Fascinating new research from a team at Yale has described a promising new Alzheimer’s treatment, developed from a half-century old antibiotic. The research suggests a drinkable cocktail composed of newly discovered polymers may disrupt the early stages of the neurodegenerative disease.
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Realizing the Potential of Gene Therapy for Neurological Disorders « The Cell and Gene Therapy Conclave

Realizing the Potential of Gene Therapy for Neurological Disorders « The Cell and Gene Therapy Conclave | Alzheimer's Disease R&D Review | Scoop.it
The New Age Banking Summit - Nigeria edition focuses on the most innovative banking trends, technologies and best practices to stay relevant in the digital age. Join senior decision makers to explore the role of fintech, omni-channel banking, digital payments and cutting-edge innovations.
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Trial of Solanezumab for Mild Dementia Due to Alzheimer’s Disease | NEJM

Trial of Solanezumab for Mild Dementia Due to Alzheimer’s Disease | NEJM | Alzheimer's Disease R&D Review | Scoop.it
Original Article from The New England Journal of Medicine — Trial of Solanezumab for Mild Dementia Due to Alzheimer’s Disease...
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Stem cell-derived neurons stop seizures and improve cognitive function

Stem cell-derived neurons stop seizures and improve cognitive function | Alzheimer's Disease R&D Review | Scoop.it
About 3.4 million Americans, or 1.2 percent of the population, have active epilepsy. Although the majority respond to medication, between 20 and 40 percent of patients with epilepsy continue to have seizures even after trying ...
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Tau impairs neural circuits, dominating amyloid-β effects, in Alzheimer models in vivo

Tau impairs neural circuits, dominating amyloid-β effects, in Alzheimer models in vivo | Alzheimer's Disease R&D Review | Scoop.it
The coexistence of amyloid-β (Aβ) plaques and tau neurofibrillary tangles in the neocortex is linked to neural system failure and cognitive decline in Alzheimer’s disease. However, the underlying neuronal mechanisms are unknown. By employing in vivo two-photon Ca2+ imaging of layer 2/3 cortical neurons in mice expressing human Aβ and tau, we reveal a dramatic tau-dependent suppression of activity and silencing of many neurons, which dominates over Aβ-dependent neuronal hyperactivity. We show that neurofibrillary tangles are neither sufficient nor required for the silencing, which instead is dependent on soluble tau. Surprisingly, although rapidly effective in tau mice, suppression of tau gene expression was much less effective in rescuing neuronal impairments in mice containing both Aβ and tau. Together, our results reveal how Aβ and tau synergize to impair the functional integrity of neural circuits in vivo and suggest a possible cellular explanation contributing to disappointing results from anti-Aβ therapeutic trials.
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Statistical analysis of multi-dimensional, temporal gene expression of stem cells to elucidate colony size-dependent neural differentiation - Molecular Omics (RSC Publishing)

Statistical analysis of multi-dimensional, temporal gene expression of stem cells to elucidate colony size-dependent neural differentiation - Molecular Omics (RSC Publishing) | Alzheimer's Disease R&D Review | Scoop.it
High throughput gene expression analysis using qPCR is commonly used to identify molecular markers of complex cellular processes. However, statistical analysis of multi-dimensional, temporal gene expression data is complicated by limited biological replicates and large number of measurements.
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IJMS | Modeling Parkinson’s Disease and Atypical Parkinsonian Syndromes Using Induced Pluripotent Stem Cells | HTML

IJMS | Modeling Parkinson’s Disease and Atypical Parkinsonian Syndromes Using Induced Pluripotent Stem Cells | HTML | Alzheimer's Disease R&D Review | Scoop.it
Parkinson’s disease (PD) and atypical parkinsonian syndromes are age-dependent multifactorial neurodegenerative diseases, which are clinically characterized by bradykinesia, tremor, muscle rigidity and postural instability.
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