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https://www.readbyqxmd.com/read/27933676/white-matter-hyperintensities-are-associated-with-disproportionate-progressive-hippocampal-atrophy
#1
Cassidy M Fiford, Emily N Manning, Jonathan W Bartlett, David M Cash, Ian B Malone, Gerard R Ridgway, Manja Lehmann, Kelvin K Leung, Carole Sudre, Sebastien Ourselin, Geert Jan Biessels, Owen T Carmichael, Nick C Fox, M Jorge Cardoso, Josephine Barnes
This study investigates relationships between white matter hyperintensity (WMH) volume, cerebrospinal fluid (CSF) Alzheimer's disease (AD) pathology markers, and brain and hippocampal volume loss. Subjects included 198 controls, 345 Mild Cognitive Impairment (MCI) and 154 AD subjects with serial volumetric 1.5T MRI. CSF Aβ42 and total tau were measured (n=353). Brain and hippocampal loss were quantified from serial MRI using the Boundary Shift Integral (BSI). Multiple linear regression models assessed the relationships between WMHs and hippocampal and brain atrophy rates...
December 9, 2016: Hippocampus
https://www.readbyqxmd.com/read/27933142/salidroside-reduces-tau-hyperphosphorylation-via-up-regulating-gsk-3%C3%AE-phosphorylation-in-a-tau-transgenic-drosophila-model-of-alzheimer-s-disease
#2
Bei Zhang, Qiongqiong Li, Xingkun Chu, Suya Sun, Shengdi Chen
BACKGROUND: Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disease that causes substantial public health care burdens. Intensive efforts have been made to find effective and safe treatment against AD. Salidroside (Sal) is the main effective component of Rhodiola rosea L., which has several pharmacological activities. The objective of this study was to investigate the efficacy of Sal in the treatment of AD transgenic Drosophila and the associated mechanisms...
2016: Translational Neurodegeneration
https://www.readbyqxmd.com/read/27931796/the-alzheimer-s-disease-neuroimaging-initiative-3-continued-innovation-for-clinical-trial-improvement
#3
REVIEW
Michael W Weiner, Dallas P Veitch, Paul S Aisen, Laurel A Beckett, Nigel J Cairns, Robert C Green, Danielle Harvey, Clifford R Jack, William Jagust, John C Morris, Ronald C Petersen, Jennifer Salazar, Andrew J Saykin, Leslie M Shaw, Arthur W Toga, John Q Trojanowski
INTRODUCTION: The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI-3, which began on August 1, 2016, is a 5-year renewal of the current ADNI-2 study. METHODS: ADNI-3 will follow current and additional subjects with normal cognition, mild cognitive impairment, and AD using innovative technologies such as tau imaging, magnetic resonance imaging sequences for connectivity analyses, and a highly automated immunoassay platform and mass spectroscopy approach for cerebrospinal fluid biomarker analysis...
December 5, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27931265/increased-caspase-6-activity-in-the-human-anterior-olfactory-nuclei-of-the-olfactory-bulb-is-associated-with-cognitive-impairment
#4
Benedicte Foveau, Steffen Albrecht, David A Bennett, José A Correa, Andrea C LeBlanc
Abnormally elevated hippocampal Caspase-6 (Casp6) activity is intimately associated with age-related cognitive impairment in humans and in mice. In humans, these high levels of Casp6 activity are initially localized in the entorhinal cortex, the area of the brain first affected by the formation of neurofibrillary tangles, according to Braak staging. The reason for the high vulnerability of entorhinal cortex neurons to neurofibrillary tangle pathology and Casp6 activity is unknown. Casp6 activity is involved in axonal degeneration, therefore, one possibility to explain increased vulnerability of the entorhinal cortex neurons would be that the afferent neurons of the olfactory bulb, some of which project their axons to the entorhinal cortex, are equally degenerating...
December 8, 2016: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/27931251/conflicting-cerebrospinal-fluid-biomarkers-and-progression-to-dementia-due-to-alzheimer-s-disease
#5
Panagiotis Alexopoulos, Lukas Werle, Jennifer Roesler, Nathalie Thierjung, Lena Sophie Gleixner, Igor Yakushev, Nikolaos Laskaris, Stefan Wagenpfeil, Philippos Gourzis, Alexander Kurz, Robert Perneczky
BACKGROUND: According to new diagnostic guidelines for Alzheimer's disease (AD), biomarkers enable estimation of the individual likelihood of underlying AD pathophysiology and the associated risk of progression to AD dementia for patients with mild cognitive impairment (MCI). Nonetheless, how conflicting biomarker constellations affect the progression risk is still elusive. The present study explored the impact of different cerebrospinal fluid (CSF) biomarker constellations on the progression risk of MCI patients...
December 9, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27930934/cognitive-remediation-for-negative-symptoms-of-schizophrenia-a-network-meta-analysis
#6
REVIEW
Matteo Cella, Antonio Preti, Clementine Edwards, Tabitha Dow, Til Wykes
Cognitive remediation (CR) is a treatment targeting cognitive difficulties in people with schizophrenia. Recent research suggested that CR may also have a positive effect on negative symptoms. This meta-analysis investigates the effect of CR on negative symptoms. A systematic search was used to identify all randomized-controlled trials of CR in people with schizophrenia reporting negative symptoms outcomes. Levels of negative symptoms at baseline, post-therapy and follow-up, sample demographics and treatment length were extracted...
November 28, 2016: Clinical Psychology Review
https://www.readbyqxmd.com/read/27929803/an-autopsy-verified-case-of-ftld-tdp-type-a-with-upper-motor-neuron-predominant-motor-neuron-disease-mimicking-mm2-thalamic-type-sporadic-creutzfeldt-jakob-disease
#7
Yuichi Hayashi, Yasushi Iwasaki, Akira Takekoshi, Nobuaki Yoshikura, Takahiko Asano, Maya Mimuro, Akio Kimura, Katsuya Satoh, Tetsuyuki Kitamoto, Mari Yoshida, Takashi Inuzuka
Here we report an autopsy-verified case of frontotemporal lobar degeneration (FTLD)-transactivation responsive region (TAR) DNA binding protein (TDP) type A with upper motor neuron-predominant motor neuron disease mimicking MM2-thalamic-type sporadic Creutzfeldt-Jakob disease (sCJD). A 69-year-old woman presented with an 11-month history of progressive dementia, irritability, insomnia, and gait disturbance without a family history of dementia or prion disease. Neurological examination revealed severe dementia, frontal signs, and exaggerated bilateral tendon reflexes...
November 2016: Prion
https://www.readbyqxmd.com/read/27929120/neurofilaments-in-blood-and-csf-for-diagnosis-and-prediction-of-onset-in-creutzfeldt-jakob-disease
#8
Petra Steinacker, Kaj Blennow, Steffen Halbgebauer, Song Shi, Viktoria Ruf, Patrick Oeckl, Armin Giese, Jens Kuhle, Dana Slivarichova, Henrik Zetterberg, Markus Otto
While cerebrospinal fluid (CSF) biomarkers for Creutzfeldt-Jakob disease (CJD) are established and partly included in the diagnostic criteria, no blood biomarkers are available. Here, we assessed the utility of serum neurofilament light chain (NF-L) and tau protein in comparison to CSF markers (NF-L and phosphorylated NF heavy chain (pNF-H), tau, S100B, 14-3-3) and prion conversion assay (real-time quaking induced conversion (RT-QuIC)) for sporadic and genetic CJD. Importantly, a Gerstmann-Sträussler-Scheinker mutation carrier in the asymptomatic phase and at disease onset was included as well...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27927959/vectored-intracerebral-immunization-with-the-anti-tau-monoclonal-antibody-phf1-markedly-reduces-tau-pathology-in-mutant-tau-transgenic-mice
#9
Wencheng Liu, Lingzhi Zhao, Brittany Blackman, Mayur Parmar, Man Ying Wong, Thomas Woo, Fangmin Yu, Dolan Sondhi, Stephen M Kaminsky, Ronald G Crystal, Steven M Paul
: Passive immunization with anti-tau monoclonal antibodies has been shown by several laboratories to reduce age-dependent tau pathology and neurodegeneration in mutant tau transgenic mice. These studies have used repeated high weekly doses of various tau antibodies administered systemically for several months and have reported reduced tau pathology of ∼40-50% in various brain regions. Here we show that direct intrahippocampal administration of the adeno-associated virus (AAV)-vectored anti-phospho-tau antibody PHF1 to P301S tau transgenic mice results in high and durable antibody expression, primarily in neurons...
December 7, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27927175/a-pilot-randomized-controlled-trial-of-a-tailored-cognitive-behavioural-therapy-based-intervention-for-depressive-symptoms-in-those-newly-diagnosed-with-multiple-sclerosis
#10
Litza A Kiropoulos, Trevor Kilpatrick, Alex Holmes, Jennifer Threader
BACKGROUND: To examine the effectiveness and acceptability of an 8-week individual tailored cognitive behavioural therapy (CBT) intervention for the treatment of depressive symptoms in those newly diagnosed with multiple sclerosis. METHODS: The current study presents a pilot, parallel group randomized controlled trial (RCT) with an allocation ratio of 1:1 conducted in a large research and teaching hospital in Melbourne, Australia. 30 individuals with a mean age of 36...
December 7, 2016: BMC Psychiatry
https://www.readbyqxmd.com/read/27926574/neural-activity-memory-and-dementias-serotonergic-markers
#11
Alfredo Meneses
Dysfunctional memory seems to be a key component of diverse dementias and other neuropsychiatric disorders; unfortunately, no effective treatment exists for this, probably because of the absence of neural biomarkers accompanying it. Diverse neurotransmission systems have been implicated in memory, including serotonin or 5-hydroxytryptamine (5-HT). There are multiple serotonergic pharmacological tools, well-characterized downstream signaling in mammals' species and neural markers providing new insights into memory functions and dysfunctions...
December 6, 2016: Behavioural Pharmacology
https://www.readbyqxmd.com/read/27926491/early-pathogenic-event-of-alzheimer-s-disease-documented-in-ipscs-from-patients-with-psen1-mutations
#12
Juan Yang, Hanzhi Zhao, Yu Ma, Guilai Shi, Jian Song, Yu Tang, Song Li, Ting Li, Nan Liu, Fan Tang, Junjie Gu, Lingling Zhang, Zhuohua Zhang, Xiaohui Zhang, Ying Jin, Weidong Le
Alzheimer's disease (AD) is the most common age-related dementia characterized by progressive neuronal loss. However, the molecular mechanisms for the neuronal loss is still debated. Here, we used induced pluripotent stem cells (iPSCs) derived from somatic cells of familial AD patients carrying PSEN1 mutations to study the early pathogenic event of AD. We found that premature neuronal differentiation with decreased proliferation and increased apoptosis occured in AD-iPSC-derived neural progenitor cells (AD-NPCs) once neuronal differentiation was initiated, together with higher levels of Aβ42 and phosphorylated tau...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27924507/tppu-protects-tau-from-h2o2-induced-hyperphosphorylation-in-hek293-tau-cells-by-regulating-pi3k-akt-gsk-3%C3%AE-pathway
#13
En-Sheng Yao, Yan Tang, Xing-Hua Liu, Ming-Huan Wang
Neurofibrillary pathology of abnormally hyperphosphorylated tau is a hallmark of Alzheimer's disease (AD) and other tauopathies. Phosphatidylinositol 3-kinase (PI3K)/Akt/glycogen synthase kinase-3 beta (GSK-3β) signaling pathway is pivotal for tau phosphorylation. Inhibition of soluble epoxide hydrolase (sEH) metabolism has been shown to effectively increase the accumulation of epoxyeicosatrienoic acids (EETs), which are cytochrome P450 metabolites of arachidonic acid and have been demonstrated to have neuroprotective effects...
December 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/27923640/the-accumulation-of-brain-injury-leads-to-severe-neuropathological-and-neurobehavioral-changes-after-repetitive-mild-traumatic-brain-injury
#14
Huabin Gao, Zhaoli Han, Ruojing Bai, Shan Huang, Xintong Ge, Fanglian Chen, Ping Lei
Traumatic brain injury (TBI) is a major public health problem with long-term neurobehavioral sequela. The evidences have revealed that TBI is a risk factor for later development of neurodegenerative disease and both the single and repetitive brain injury can lead to the neurodegeneration. But whether the effects of accumulation play an important role in the neurodegenerative disease is still unknown. We utilized the Sprague Dawley (SD) rats to develop the animal models of repetitive mild TBI and single mild TBI in order to detect the neurobehavioral changes...
December 3, 2016: Brain Research
https://www.readbyqxmd.com/read/27923413/impact-of-enriched-environment-on-production-of-tau-amyloid-precursor-protein-and-amyloid-%C3%AE-peptide-in-high-fat-and-high-sucrose-fed-rats
#15
Yavuz Selvi, Hasan Serdar Gergerlioglu, Nursel Akbaba, Mehmet Oz, Ali Kandeger, Enver Ahmet Demir, Fatma Humeyra Yerlikaya, Kismet Esra Nurullahoglu-Atalik
OBJECTIVE: The Western-type diet is associated with an elevated risk of Alzheimer's disease and other milder forms of cognitive impairment. The aim of the present study was to investigate the effects of the environmental enrichment on amyloid and tau pathology in high-fat and high-sucrose-fed rats. METHODS: In total, 40 adult male rats were categorised into two main groups according to their housing conditions: enriched environment (EE, n=16) and standard housing condition (n=24)...
December 7, 2016: Acta Neuropsychiatrica
https://www.readbyqxmd.com/read/27922637/a-human-carboxypeptidase-e-nf-%C3%AE-1-gene-mutation-in-an-alzheimer-s-disease-patient-leads-to-dementia-and-depression-in-mice
#16
Y Cheng, N X Cawley, T Yanik, S R K Murthy, C Liu, F Kasikci, D Abebe, Y P Loh
Patients with Alzheimer's disease (AD), a common dementia among the aging population, often also suffer from depression. This comorbidity is poorly understood. Although most forms of AD are not genetically inherited, we have identified a new human mutation in the carboxypeptidase E (CPE)/neurotrophic factor-α1 (NF-α1) gene from an AD patient that caused memory deficit and depressive-like behavior in transgenic mice. This mutation consists of three adenosine inserts, introducing nine amino acids, including two glutamines into the mutant protein, herein called CPE-QQ...
December 6, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27919234/blended-cbt-versus-face-to-face-cbt-a-randomised-non-inferiority-trial
#17
Kim Mathiasen, Tonny E Andersen, Heleen Riper, Annet A M Kleiboer, Kirsten K Roessler
BACKGROUND: Internet based cognitive behavioural therapy (iCBT) has been demonstrated to be cost- and clinically effective. There is a need, however, for increased therapist contact for some patient groups. Combining iCBT with traditional face-to-face (ftf) consultations in a blended format (B-CBT) may produce a new treatment format with multiple benefits from both traditional CBT and iCBT such as individual adaptation, lower costs than traditional therapy, wide geographical and temporal availability, and possibly lower threshold to implementation...
December 5, 2016: BMC Psychiatry
https://www.readbyqxmd.com/read/27917428/ftir-imaging-of-the-molecular-burden-around-a%C3%AE-deposits-in-an-early-stage-3-tg-app-psp1-tau-mouse-model-of-alzheimer-s-disease
#18
Artur Dawid Surowka, Michael Pilling, Alex Henderson, Herve Boutin, Lidan Christie, Magdalena Szczerbowska-Boruchowska, Peter Gardner
Alzheimer's disease is one of the major causes of dementia in the elderly. The disease is caused by the misfolding of water soluble alpha-helical proteins, which leads to the accumulation of β-sheets in the form of amyloid plaques, which can subsequently affect surrounding tissue areas by oxidative stress neurotoxicity. The aim of the present study was to design a novel methodology to analyze the extent to the neuronal burden around protein-rich Aβ plaques suspected to affect molecular components by oxidative stress induced by inflammatory states...
December 5, 2016: Analyst
https://www.readbyqxmd.com/read/27916654/prion-like-mechanisms-and-potential-therapeutic-targets-in-neurodegenerative-disorders
#19
REVIEW
Masato Hasegawa, Takashi Nonaka, Masami Masuda-Suzukake
Prion-like propagation of abnormal intracytoplasmic proteins, which are the defining features of major neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), has been proposed. A growing body of evidence strongly suggests that abnormal tau, α-synuclein and TDP-43 have prion-like properties, convert the corresponding normal proteins into abnormal forms, and are transmitted from cell to cell, spreading throughout the brain. This idea is extremely important not only for understanding the pathogenesis and progression of these diseases, but also for the development of molecular therapies...
December 1, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27916386/beneficial-effect-of-bilingualism-on-alzheimer-s-disease-csf-biomarkers-and-cognition
#20
Ainara Estanga, Mirian Ecay-Torres, Almudena Ibañez, Andrea Izagirre, Jorge Villanua, Maite Garcia-Sebastian, M Teresa Iglesias Gaspar, Ane Otaegui-Arrazola, Ane Iriondo, Monserrat Clerigue, Pablo Martinez-Lage
Bilingualism as a component of cognitive reserve has been claimed to delay the onset of Alzheimer's disease (AD). However, its effect on cerebrospinal fluid (CSF) AD-biomarkers has not been investigated. We assessed cognitive performance and CSF AD-biomarkers, and potential moderation effect of bilingualism on the association between age, CSF AD-biomarkers, and cognition. Cognitively healthy middle-aged participants classified as monolinguals (n = 100, nCSF = 59), early (n = 81, nCSF = 55) and late bilinguals (n = 97, nCSF = 52) were evaluated...
December 1, 2016: Neurobiology of Aging
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