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https://www.readbyqxmd.com/read/29353455/the-interplay-between-apolipoprotein-e4-and-the-autophagic-endocytic-lysosomal-axis
#1
REVIEW
E Schmukler, D M Michaelson, R Pinkas-Kramarski
Since its discovery as a genetic risk factor for Alzheimer's disease, the APOE4 allele has been linked to the majority of the pathological findings associated with the disease progression. These include abnormalities of the endocytic, autophagic, and lysosomal machineries, which begin at the most early stages of Alzheimer's disease development. Considering that these three vesicular systems share common features and, in fact, comprise an interconnected cargo-trafficking and degradation network, some of the effects of APOE4 are interrelated, while others are system-specific...
January 20, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29353355/cerebrospinal-fluid-biomarkers-profile-of-idiopathic-normal-pressure-hydrocephalus
#2
REVIEW
Tommaso Schirinzi, Giulia Maria Sancesario, Giulia Di Lazzaro, Alessio D'Elia, Paola Imbriani, Simona Scalise, Antonio Pisani
Idiopathic normal pressure hydrocephalus (iNPH) is a disabling neurological disorder whose potential treatability is significantly limited by diagnostic uncertainty. In fact, typical clinical presentation occurs at late phases of disease, when CSF shunting could be ineffective. In recent years, measurement of different CSF proteins, whose concentration directly reflects neuropathological changes of CNS, has significantly improved both diagnostic timing and accuracy of neurodegenerative disease. Unfortunately iNPH lacks neuropathological hallmarks allowing the identification of specific disease biomarkers...
January 20, 2018: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29353232/albuminuria-increases-the-risks-for-both-alzheimer-disease-and-vascular-dementia-in-community-dwelling-japanese-elderly-the-hisayama-study
#3
Keita Takae, Jun Hata, Tomoyuki Ohara, Daigo Yoshida, Mao Shibata, Naoko Mukai, Yoichiro Hirakawa, Hiro Kishimoto, Kazuhiko Tsuruya, Takanari Kitazono, Yutaka Kiyohara, Toshiharu Ninomiya
BACKGROUND: Epidemiologic evidence has emerged to reveal an association of albuminuria and low estimated glomerular filtration rate (eGFR) with dementia, but the findings are inconsistent. In addition, there are limited studies addressing the association between albuminuria and Alzheimer disease (AD). METHODS AND RESULTS: A total of 1562 community-dwelling Japanese subjects aged ≥60 years without dementia were followed up for 10 years. The outcomes were incidence of all-cause dementia and its subtypes, namely, AD and vascular dementia (VaD)...
January 20, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29353102/aging-african-green-monkeys-manifest-transcriptional-pathological-and-cognitive-hallmarks-of-human-alzheimer-s-disease
#4
Paige E Cramer, Renee C Gentzel, Keith Q Tanis, Joshua Vardigan, Yi Wang, Brett Connolly, Philip Manfre, Kenneth Lodge, John J Renger, Celina Zerbinatti, Jason M Uslaner
While many preclinical models of Alzheimer's disease (AD) have been reported, none fully recapitulate the disease. In an effort to identify an appropriate preclinical disease model, we characterized age-related changes in 2 higher order species, the African green monkey (AGM) and the rhesus macaque. Gene expression profiles in the dorsolateral prefrontal cortex and the visual cortex showed age-related changes in AGMs that are strikingly reminiscent of AD, whereas aged rhesus were most similar to healthy elderly humans...
December 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29353101/amyloid-pathology-in-the-progression-to-mild-cognitive-impairment
#5
Philip S Insel, Oskar Hansson, R Scott Mackin, Michael Weiner, Niklas Mattsson
The objective of this study was to determine the cognitive and functional decline and development of brain injury in individuals progressing from preclinical (β-amyloid positive cognitively normal) to prodromal Alzheimer's disease (AD) (β-amyloid positive mild cognitive impairment [MCI]), and compare this with individuals who progress to MCI in the absence of significant amyloid pathology. Seventy-five cognitively healthy participants who progressed to MCI were followed for 4 years on average and up to 10 years...
December 27, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29353063/dipeptidyl-peptidase-iv-which-probably-plays-important-roles-in-alzheimer-disease-ad-pathology-is-upregulated-in-ad-brain-neurons-and-associates-with-amyloid-plaques
#6
Hans-Gert Bernstein, Henrik Dobrowolny, Gerburg Keilhoff, Johann Steiner
There is evidence from in vitro experiments that dipeptidyl peptidase IV (DPP IV) might play role(s) in amyloid formation. However, nothing is known about the localization of the enzyme in brains of individuals with Alzheimer's disease. We herein show that in comparison to non-demented controls DPP IV is upregulated in AD brain neurons and occurs in multiple amyloid plaques.
January 16, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29353052/evidence-for-altered-insulin-receptor-signaling-in-alzheimer-s-disease
#7
REVIEW
Chelsea M Griffith, Tore Eid, Gregory M Rose, Peter R Patrylo
Epidemiological data have shown that metabolic disease can increase the propensity for developing cognitive decline and dementia, particularly Alzheimer's disease (AD). While this interaction is not completely understood, clinical studies suggest that both hyper- and hypoinsulinemia are associated with an increased risk for developing AD. Indeed, insulin signaling is altered in post-mortem brain tissue from AD patients and treatments known to enhance insulin signaling, can improve cognitive function. Further, clinical evidence has shown that AD patients and mouse models of AD often display alterations in peripheral metabolism...
January 15, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29352996/-plasticity-molecule-reveals-interneuronal-alterations-in-alzheimer-s-disease
#8
EDITORIAL
Juan Nacher
No abstract text is available yet for this article.
January 15, 2018: Neuroscience
https://www.readbyqxmd.com/read/29352978/use-of-multimodality-imaging-and-artificial-intelligence-for-diagnosis-and-prognosis-of-early-stages-of-alzheimer-s-disease
#9
REVIEW
Xiaonan Liu, Kewei Chen, Teresa Wu, David Weidman, Fleming Lure, Jing Li
Alzheimer's disease (AD) is a major neurodegenerative disease and the most common cause of dementia. Currently, no treatment exists to slow down or stop the progression of AD. There is converging belief that disease-modifying treatments should focus on early stages of the disease, that is, the mild cognitive impairment (MCI) and preclinical stages. Making a diagnosis of AD and offering a prognosis (likelihood of converting to AD) at these early stages are challenging tasks but possible with the help of multimodality imaging, such as magnetic resonance imaging (MRI), fluorodeoxyglucose-positron emission topography (PET), amyloid-PET, and recently introduced tau-PET, which provides different but complementary information...
January 10, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29352507/nuclear-and-membrane-estrogen-receptor-antagonists-induce-similar-mtorc2-activation-reversible-changes-in-synaptic-protein-expression-and-actin-polymerization-in-the-mouse-hippocampus
#10
Fang-Zhou Xing, Yan-Gang Zhao, Yuan-Yuan Zhang, Li He, Ji-Kai Zhao, Meng-Ying Liu, Yan Liu, Ji-Qiang Zhang
AIMS: Estrogens play pivotal roles in hippocampal synaptic plasticity through nuclear receptors (nERs; including ERα and ERβ) and the membrane receptor (mER; also called GPR30), but the underlying mechanism and the contributions of nERs and mER remain unclear. Mammalian target of rapamycin complex 2 (mTORC2) is involved in actin cytoskeleton polymerization and long-term memory, but whether mTORC2 is involved in the regulation of hippocampal synaptic plasticity by ERs is unclear. METHODS: We treated animals with nER antagonists (MPP/PHTPP) or the mER antagonist (G15) alone or in combination with A-443654, an activator of mTORC2...
January 19, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29352484/melatonin-ameliorates-a%C3%AE-42-induced-alteration-of-%C3%AE-app-processing-secretases-via-the-melatonin-receptor-through-the-pin1-gsk3%C3%AE-nf-%C3%AE%C2%BAb-pathway-in-sh-sy5y-cells
#11
Vorapin Chinchalongporn, Mayuri Shukla, Piyarat Govitrapong
Melatonin is involved in the physiological regulation of the β- amyloid precursor protein (βAPP) cleaving secretases which are responsible for generation of the neurotoxic amyloid beta (Aβ) peptide, one of the hallmarks of Alzheimer's disease (AD) pathology. In this study, we aimed to determine the underlying mechanisms of this regulation under pathological conditions. We establish that melatonin prevents Aβ42 -induced down-regulation of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) as well as up-regulation of β-site APP-cleaving enzyme 1 (BACE1) and presenilin 1 (PS1) in SH-SY5Y cell cultures...
January 20, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29352444/activation-of-the-anti-aging-and-cognition-enhancing-gene-klotho-by-crispr-dcas9-transcriptional-effector-complex
#12
Ci-Di Chen, Ella Zeldich, Yuexuan Li, Andrea Yuste, Carmela R Abraham
Multiple lines of evidence show that the anti-aging and cognition-enhancing protein Klotho fosters neuronal survival, increases the anti-oxidative stress defense, and promotes remyelination of demyelinated axons. Thus, upregulation of the Klotho gene can potentially alleviate the symptoms and/or prevent the progression of age-associated neurodegenerative diseases such as Alzheimer's disease and demyelinating diseases such as multiple sclerosis. Here we used a CRISPR-dCas9 complex to investigate single-guide RNA (sgRNA) targeting the Klotho promoter region for efficient transcriptional activation of the Klotho gene...
January 19, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29352390/a-spatial-registration-toolbox-for-structural-mr-imaging-of-the-aging-brain
#13
Marco Ganzetti, Quanying Liu, Dante Mantini
During aging the brain undergoes a series of structural changes, in size, shape as well as tissue composition. In particular, cortical atrophy and ventricular enlargement are often present in the brain of elderly individuals. This poses serious challenges in the spatial registration of structural MR images. In this study, we addressed this open issue by proposing an enhanced framework for MR registration and segmentation. Our solution was compared with other approaches based on the tools available in SPM12, a widely used software package...
January 19, 2018: Neuroinformatics
https://www.readbyqxmd.com/read/29352267/differential-susceptibility-of-striatal-hippocampal-and-cortical-neurons-to-caspase-6
#14
Anastasia Noël, Libin Zhou, Bénédicte Foveau, P Jesper Sjöström, Andréa C LeBlanc
Active cysteinyl protease Caspase-6 is associated with early Alzheimer and Huntington diseases. Higher entorhinal cortex and hippocampal Caspase-6 levels correlate with lower cognitive performance in aged humans. Caspase-6 induces axonal degeneration in human primary neuron cultures and causes inflammation and neurodegeneration in mouse hippocampus, and age-dependent memory impairment. To assess whether Caspase-6 causes damage to another neuronal system, a transgenic knock-in mouse overexpressing a self-activated form of Caspase-6 five-fold in the striatum, the area affected in Huntington disease, and 2...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352259/plasma-mcp-1-and-cognitive-decline-in-patients-with-alzheimer-s-disease-and-mild-cognitive-impairment-a-two-year-follow-up-study
#15
Wei-Ju Lee, Yi-Chu Liao, Yen-Feng Wang, I-Feng Lin, Shuu-Jiun Wang, Jong-Ling Fuh
Monocyte chemoattractant protein-1 (MCP-1, also known as chemokine CCL2) is a vital chemokine that mediates inflammation in Alzheimer's disease (AD). We analyzed the associations between the baseline plasma MCP-1 level, longitudinal cognitive changes, and genetic effects of CCL2 rs1024611 and its receptor, CC-chemokine receptor 2 (CCR2) rs1799864, in AD. In total, 310 AD patients and 66 mild cognitive impairment (MCI) patients were followed for 2 years, and 120 controls were recruited at baseline for comparison...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352234/bi-exponential-3d-t1%C3%AF-mapping-of-whole-brain-at-3%C3%A2-t
#16
Rajiv G Menon, Azadeh Sharafi, Johannes Windschuh, Ravinder R Regatte
Detection of multiple relaxation pools using MRI is useful in a number of neuro-pathologies including multiple sclerosis (MS), Alzheimer's, and stroke. In this study we evaluate the feasibility of using T1ρ imaging for the detection of bi-exponential decays in the human brain. A prospective T1ρ imaging study was performed on model relaxation phantoms (eggs) and 7 healthy volunteers. The data was fitted using a single pool and a 2-pool model to estimate mono- and bi-exponential T1ρ maps, respectively. Bi-exponential decays were identified in the gray matter (GM) and white matter (WM) of the brain with 40...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29351877/rest-a-master-transcriptional-regulator-in-neurodegenerative-disease
#17
REVIEW
Jee-Yeon Hwang, R Suzanne Zukin
The restrictive element-1 silencing transcription factor)/NRSF (neuron-restrictive silencing factor (NRSF) is a transcriptional repressor which acts via epigenetic remodeling to silence target genes. Emerging evidence indicates that REST is a master transcriptional regulator of neuron-specific genes not only in neurogenesis and neuronal differentiation, but also in differentiated neurons during the critical period in postnatal brain development, where it plays a role in fine-tuning of genes involved in synaptic plasticity, and in normal aging, where it promotes neuroprotection by repressing genes involved in oxidative stress and β-amyloid toxicity...
January 16, 2018: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29351720/structural-interconversion-in-alzheimer-s-amyloid-%C3%AE-16-35-peptide-in-an-aqueous-solution
#18
Nelson Alves, Rafael B Frigori
Structural properties of Aβ(16-35) fragment are investigated as a model for the amyloid-β peptide excluding its coil-inducing terminals. Our Replica-Exchange Molecular Dynamics simulations using all-atoms and explicit aqueous solvation widely reduce any structural bias. The principal folding pathway shows direct conversion of coil to β-sheet, without the long proposed helix intermediates. Our PCA analysis indicates that the fragment is also intrinsically disordered, as the full amyloid-β peptide. Thus, the observed folding mechanism lacks free-energy barriers and any peaks in the thermal capacity...
January 19, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29351627/repair-kinetics-of-dna-double-strand-breaks-and-incidence-of-apoptosis-in-mouse-neural-stem-progenitor-cells-and-their-differentiated-neurons-exposed-to-ionizing-radiation
#19
Hiroki Kashiwagi, Kazunori Shiraishi, Kenta Sakaguchi, Tomoya Nakahama, Seiji Kodama
Neuronal loss leads to neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease and Huntington's disease. Because of their long lifespans, neurons are assumed to possess highly efficient DNA repair ability and to be able to protect themselves from deleterious DNA damage such as DNA double-strand breaks (DSBs) produced by intrinsic and extrinsic sources. However, it remains largely unknown whether the DSB repair ability of neurons is more efficient compared with that of other cells. Here, we investigated the repair kinetics of X-ray-induced DSBs in mouse neural cells by scoring the number of phosphorylated 53BP1 foci post irradiation...
January 17, 2018: Journal of Radiation Research
https://www.readbyqxmd.com/read/29351585/core-differences-in-synaptic-signaling-between-primary-visual-and-dorsolateral-prefrontal-cortex
#20
Sheng-Tao Yang, Min Wang, Constantinos D Paspalas, Johanna L Crimins, Marcus T Altman, James A Mazer, Amy F T Arnsten
Neurons in primary visual cortex (V1) are more resilient than those in dorsolateral prefrontal cortex (dlPFC) in aging, schizophrenia and Alzheimer's disease. The current study compared glutamate and neuromodulatory actions in macaque V1 to those in dlPFC, and found striking regional differences. V1 neuronal firing to visual stimuli depended on AMPA receptors, with subtle NMDA receptor contributions, while dlPFC depends primarily on NMDA receptors. Neuromodulatory actions also differed between regions. In V1, cAMP signaling increased neuronal firing, and the phosphodiesterase PDE4A was positioned to regulate cAMP effects on glutamate release from axons...
January 17, 2018: Cerebral Cortex
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