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https://www.readbyqxmd.com/read/28212403/cerebrospinal-fluid-biomarkers-of-infantile-congenital-hydrocephalus
#1
David D Limbrick, Brandon Baksh, Clinton D Morgan, Gakwaya Habiyaremye, James P McAllister, Terrie E Inder, Deanna Mercer, David M Holtzman, Jennifer Strahle, Michael J Wallendorf, Diego M Morales
INTRODUCTION: Hydrocephalus is a complex neurological disorder with a pervasive impact on the central nervous system. Previous work has demonstrated derangements in the biochemical profile of cerebrospinal fluid (CSF) in hydrocephalus, particularly in infants and children, in whom neurodevelopment is progressing in parallel with concomitant neurological injury. The objective of this study was to examine the CSF of children with congenital hydrocephalus (CHC) to gain insight into the pathophysiology of hydrocephalus and identify candidate biomarkers of CHC with potential diagnostic and therapeutic value...
2017: PloS One
https://www.readbyqxmd.com/read/28211810/therapeutics-of-neurotransmitters-in-alzheimer-s-disease
#2
Ramesh Kandimalla, P Hemachandra Reddy
Alzheimer's disease (AD) is a progressive neurodegenerative disease, characterized by the loss of memory, multiple cognitive impairments and changes in the personality and behavior. Several decades of intense research have revealed that multiple cellular changes are involved in disease process, including synaptic damage, mitochondrial abnormalities and inflammatory responses, in addition to formation and accumulation of amyloid-β (Aβ) and phosphorylated tau. Although tremendous progress has been made in understanding the impact of neurotransmitters in the progression and pathogenesis of AD, we still do not have a drug molecule associated with neurotransmitter(s) that can delay disease process in elderly individuals and/or restore cognitive functions in AD patients...
February 15, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28209725/soluble-trem2-induces-inflammatory-responses-and-enhances-microglial-survival
#3
Li Zhong, Xiao-Fen Chen, Tingting Wang, Zhe Wang, Chunyan Liao, Zongqi Wang, Ruizhi Huang, Daxin Wang, Xinxiu Li, Linbei Wu, Lin Jia, Honghua Zheng, Meghan Painter, Yuka Atagi, Chia-Chen Liu, Yun-Wu Zhang, John D Fryer, Huaxi Xu, Guojun Bu
Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor expressed in microglia in the brain. A soluble form of TREM2 (sTREM2) derived from proteolytic cleavage of the cell surface receptor is increased in the preclinical stages of AD and positively correlates with the amounts of total and phosphorylated tau in the cerebrospinal fluid. However, the physiological and pathological functions of sTREM2 remain unknown. Here, we show that sTREM2 promotes microglial survival in a PI3K/Akt-dependent manner and stimulates the production of inflammatory cytokines depending on NF-κB...
February 16, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28205010/prion-specific-and-surrogate-csf-biomarkers-in-creutzfeldt-jakob-disease-diagnostic-accuracy-in-relation-to-molecular-subtypes-and-analysis-of-neuropathological-correlates-of-p-tau-and-a%C3%AE-42-levels
#4
Francesca Lattanzio, Samir Abu-Rumeileh, Alessia Franceschini, Hideaki Kai, Giulia Amore, Ilaria Poggiolini, Marcello Rossi, Simone Baiardi, Lynne McGuire, Anna Ladogana, Maurizio Pocchiari, Alison Green, Sabina Capellari, Piero Parchi
The differential diagnosis of Creutzfeldt-Jakob disease (CJD) from other, sometimes treatable, neurological disorders is challenging, owing to the wide phenotypic heterogeneity of the disease. Real-time quaking-induced prion conversion (RT-QuIC) is a novel ultrasensitive in vitro assay, which, at variance with surrogate neurodegenerative biomarker assays, specifically targets the pathological prion protein (PrP(Sc)). In the studies conducted to date in CJD, cerebrospinal fluid (CSF) RT-QuIC showed good diagnostic sensitivity (82-96%) and virtually full specificity...
February 15, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28202389/targeting-the-hdac2-hnf-4a-mir-101b-ampk-pathway-rescues-tauopathy-and-dendritic-abnormalities-in-alzheimer-s-disease
#5
Dan Liu, Hui Tang, Xin-Yan Li, Man-Fei Deng, Na Wei, Xiong Wang, Ya-Fan Zhou, Ding-Qi Wang, Peng Fu, Jian-Zhi Wang, Sébastien S Hébert, Jian-Guo Chen, Youming Lu, Ling-Qiang Zhu
Histone deacetylase 2 (HDAC2) plays a major role in the epigenetic regulation of gene expression. Previous studies have shown that HDAC2 expression is strongly increased in Alzheimer's disease (AD), a major neurodegenerative disorder and the most common form of dementia. Moreover, previous studies have linked HDAC2 to Aβ overproduction in AD; however, its involvement in tau pathology and other memory-related functions remains unclear. Here, we show that increased HDAC2 levels strongly correlate with phosphorylated tau in a mouse model of AD...
February 12, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28196768/cerebrospinal-fluid-markers-detect-alzheimer-s-disease-in-nonamnestic-dementia
#6
Carly Oboudiyat, Tamar Gefen, Eleni Varelas, Sandra Weintraub, Emily Rogalski, Eileen H Bigio, M-Marsel Mesulam
INTRODUCTION: The accuracy of cerebrospinal fluid (CSF) biomarkers for detecting Alzheimer's disease (AD) pathology has not been fully validated in autopsied nonamnestic dementias. METHODS: We retrospectively evaluated CSF β-amyloid 1-42, phosphorylated-tau, and amyloid-tau index as predictors of Alzheimer pathology in patients with primary progressive aphasia, frontotemporal dementia, and progressive supranuclear palsy. RESULTS: Nineteen nonamnestic autopsied cases with relevant CSF values were included...
February 11, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28191467/effects-of-tibolone-on-the-central-nervous-system-clinical-and-experimental-approaches
#7
REVIEW
Rodolfo Pinto-Almazán, Julia J Segura-Uribe, Eunice D Farfán-García, Christian Guerra-Araiza
Hormone replacement therapy (HRT) increases the risk of endometrial and breast cancer. A strategy to reduce this incidence is the use of tibolone (TIB). The aim of this paper was to address the effects of TIB on the central nervous system (CNS). For the present review, MEDLINE (via PubMed), LILACS (via BIREME), Ovid Global Health, SCOPUS, Scielo, and PsycINFO (ProQuest Research Library) electronic databases were searched for the results of controlled clinical trials on peri- and postmenopausal women published from 1990 to September 2016...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28181072/interactions-of-mitochondria-metabolism-and-calcium-regulation-in-alzheimer-s-disease-a-calcinist-point-of-view
#8
Gary E Gibson, Ankita Thakkar
Decades of research suggest that alterations in calcium are central to the pathophysiology of Alzheimer's Disease (AD). Highly reproducible changes in calcium dynamics occur in cells from patients with both genetic and non-genetic forms of AD relative to controls. The most robust change is an exaggerated release of calcium from internal stores. Detailed analysis of these changes in animal and cell models of the AD-causing presenilin mutations reveal robust changes in ryanodine receptors, inositol tris-phosphate receptors, calcium leak channels and store activated calcium entry...
February 8, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28181005/the-pseudomonas-aeruginosa-exoenzyme-y-a-promiscuous-nucleotidyl-cyclase-edema-factor-and-virulence-determinant
#9
K Adam Morrow, Dara W Frank, Ron Balczon, Troy Stevens
Exoenzyme Y (ExoY) was identified as a component of the Pseudomonas aeruginosa type 3 secretion system secretome in 1998. It is a common contributor to the arsenal of type 3 secretion system effectors, as it is present in approximately 90% of Pseudomonas isolates. ExoY has adenylyl cyclase activity that is dependent upon its association with a host cell cofactor. However, recent evidence indicates that ExoY is not just an adenylyl cyclase; rather, it is a promiscuous cyclase capable of generating purine and pyrimidine cyclic nucleotide monophosphates...
February 9, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28179468/neurofilament-as-a-blood-marker-for-diagnosis-and-monitoring-of-primary-progressive-aphasias
#10
Petra Steinacker, Elisa Semler, Sarah Anderl-Straub, Janine Diehl-Schmid, Matthias L Schroeter, Ingo Uttner, Hans Foerstl, Bernhard Landwehrmeyer, Christine A F von Arnim, Jan Kassubek, Patrick Oeckl, Hans-Jürgen Huppertz, Klaus Fassbender, Klaus Fliessbach, Johannes Prudlo, Carola Roßmeier, Johannes Kornhuber, Anja Schneider, Alexander E Volk, Martin Lauer, Adrian Danek, Albert C Ludolph, Markus Otto
OBJECTIVE: To assess the utility of serum neurofilament for diagnosis and monitoring of primary progressive aphasia (PPA) variants. METHODS: We investigated neurofilament light chain (NF-L) levels in blood of 99 patients with PPA (40 with nonfluent variant PPA [nfvPPA], 38 with semantic variant PPA [svPPA], 21 with logopenic variant PPA [lvPPA]) and compared diagnostic performance with that reached by CSF NF-L, phosphorylated neurofilament heavy chain (pNF-H), β-amyloid (Aβ1-42), tau, and phosphorylated tau...
February 8, 2017: Neurology
https://www.readbyqxmd.com/read/28176663/gsk3%C3%AE-5-flanking-dna-methylation-and-expression-in-alzheimer-s-disease-patients
#11
Vincenzina Nicolia, Viviana Ciraci, Rosaria A Cavallaro, Isidre Ferrer, Sigfrido Scarpa, Andrea Fuso
BACKGROUND: The GSK3β has been associated to pathological functions in neurodegenerative diseases. This kinase is involved in hyperphosphorylation of microtubule-associated tau protein, leading to aggregation andformation of NFTs.It has clearly been shown that GSK3β is regulated at post-translational level: phosphorylation at Tyr216 activates kinase while phosphorylation at Ser9 is essential to inhibit its activity. OBJECTIVES: At present, there are contradictory findings about the possibility that GSK3β may be regulated at gene level...
February 3, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28176624/vitamin-d-combined-with-resveratrol-prevents-cognitive-decline-in-samp8-mice
#12
Jinbo Cheng, Yehua Rui, Liqiang Qin, Jiaying Xu, Shufen Han, Linxi Yuan, Xuebin Yin, Zhongxiao Wan
Background Vitamin D (VD) and resveratrol (RSV) are two nutritional molecules that have reported neuroprotective effects, and findings from cellular models suggest that resveratrol could potentiate vitamin D's effects. The senescence-accelerated mouse-prone 8 (SAMP8) is a useful model of Alzheimer's disease (AD)-related memory impairment. Objective We aimed to explore how the combination of vitamin D with resveratrol would affect memory impairments shown by SAMP8 mice, as well as the potential mechanisms...
February 6, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28173111/reduced-dynamin-related-protein-1-protects-against-phosphorylated-tau-induced-mitochondrial-dysfunction-and-synaptic-damage-in-alzheimer-s-disease
#13
Ramesh Kandimalla, Maria Manczak, David Fry, Yeguvapalli Suneetha, Hiromi Sesaki, P Hemachandra Reddy
No abstract text is available yet for this article.
November 15, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28168741/comparison-of-at8-immunoreactivity-in-the-locus-ceruleus-and-hippocampus-of-154-brains-from-routine-autopsies
#14
Koichi Okamoto, Masakuni Amari, Toshio Fukuda, Keiji Suzuki, Masamitsu Takatama
We compared semiquantitatively AT8 immunoreactivity in the locus ceruleus (LC) and hippocampus of 154 brains from routine autopsies to investigate the initial sites of phosphorylated tau (phospho-tau) development. The numbers of AT8-positive neurons and the severity of AT8-positive neuropil threads (NTs) in the LC were strongly associated: there were no cases with AT8-positive neurons that lacked NTs and 20 cases (13%) had only NTs in the LC. Phospho-tau pathologies in the LC were almost equally on both sides, although some cases (7...
February 6, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28166276/homovanillic-acid-and-5-hydroxyindole-acetic-acid-as-biomarkers-for-dementia-with-lewy-bodies-and-coincident-alzheimer-s-disease-an-autopsy-confirmed-study
#15
Satoru Morimoto, Masaki Takao, Hiroyuki Hatsuta, Yasushi Nishina, Tadashi Komiya, Renpei Sengoku, Yuta Nakano, Akiko Uchino, Hiroyuki Sumikura, Yuko Saito, Kazutomi Kanemaru, Shigeo Murayama
Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are the two most common causes of dementia. Both pathologies often coexist, and AD patients with concomitant neocortical LB pathology (referred to as the Lewy body variant of AD) generally show faster cognitive decline and accelerated mortality relative to patients with pure AD. Thus, discriminating among patients with DLB, AD, and coincident DLB and AD is important in clinical practice. We examined levels of homovanillic acid (HVA), 5-hydroxyindole acetic acid (5-HIAA), tau, phosphorylated tau (p-tau), and beta-amyloid (Aβ) 1-42 in cerebrospinal fluid (CSF) to evaluate their viability as biomarkers to discriminate among different forms of dementia...
2017: PloS One
https://www.readbyqxmd.com/read/28160413/accelerated-aging-exacerbates-a-pre-existing-pathology-in-a-tau-transgenic-mouse-model
#16
Liviu-Gabriel Bodea, Harrison Tudor Evans, Ann Van der Jeugd, Lars M Ittner, Fabien Delerue, Jillian Kril, Glenda Halliday, John Hodges, Mathew C Kiernan, Jürgen Götz
Age is a critical factor in the prevalence of tauopathies, including Alzheimer's disease. To observe how an aging phenotype interacts with and affects the pathological intracellular accumulation of hyperphosphorylated tau, the tauopathy mouse model pR5 (expressing P301L mutant human tau) was back-crossed more than ten times onto a senescence-accelerated SAMP8 background to establish the new strain, SApT. Unlike SAMP8 mice, pR5 mice are characterized by a robust tau pathology particularly in the amygdala and hippocampus...
February 4, 2017: Aging Cell
https://www.readbyqxmd.com/read/28157099/sex-impact-on-tau-aggregation-and-postsynaptic-protein-levels-in-the-p301l-mouse-model-of-tauopathy
#17
Lucia Buccarello, Giuliano Grignaschi, Anna Maria Castaldo, Alessia Di Giancamillo, Cinzia Domeneghini, Roberto Cosimo Melcangi, Tiziana Borsello
P301L transgenic (tg) mice well mimic features of human tauopathies and provide a good model for investigating the role of tau in neurodegenerative events. We here analyzed the possible interaction among phosphorylation of tau (p-tau), spine injury, neuronal death, and sex in the P301L mouse model of tauopathy. When compared to control mice (ctr), P301L transgenic mice (tg) presented with lower body weight, reduced survival rate, hyperphosphorylated tau, spine injury, and neuronal loss in both cerebral cortex and hippocampus at 15 months of age...
February 1, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28157094/treadmill-exercise-exerts-neuroprotection-and-regulates-microglial-polarization-and-oxidative-stress-in-a-streptozotocin-induced-rat-model-of-sporadic-alzheimer-s-disease
#18
Yujiao Lu, Yan Dong, Donovan Tucker, Ruimin Wang, Mohammad Ejaz Ahmed, Darrell Brann, Quanguang Zhang
Recent work has suggested that exercise may be beneficial in preventing or ameliorating symptoms of several neurological disorders, although the mechanism is not entirely understood. The current study was designed to examine the potential beneficial effect of treadmill exercise upon cognitive function in a streptozotocin (STZ)-induced rat model of Alzheimer's disease (AD). Animals underwent treadmill exercise (30 min/day, 5 days/week) for 4 weeks after bilateral STZ intracerebroventricular injection (2.4 mg/kg)...
February 1, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28157093/bace1-dynamics-upon-inhibition-with-a-bace-inhibitor-and-correlation-to-downstream-alzheimer-s-disease-markers-in-elderly-healthy-participants
#19
Maarten Timmers, Soraia Barão, Bianca Van Broeck, Ina Tesseur, John Slemmon, Katja De Waepenaert, Jennifer Bogert, Leslie M Shaw, Sebastiaan Engelborghs, Dieder Moechars, Marc Mercken, Luc Van Nueten, Luc Tritsmans, Bart de Strooper, Johannes Rolf Streffer
The β-site amyloid-β protein precursor (AβPP) cleaving enzyme-1 (BACE1) is the rate limiting enzyme in the generation of amyloid-β peptide (Aβ) from AβPP, one of the major pathways in Alzheimer's disease (AD) pathology. Increased BACE1 levels and activity have been reported in the brain of patients with sporadic AD. Therefore, changes of BACE1 levels in the cerebrospinal fluid (CSF) have also been investigated as a possible biomarker of the disease. We analyzed BACE1 levels in CSF of elderly healthy participants before and after chronic treatment with a BACE inhibitor (BACEi) and evaluated the correlation between BACE1 levels and downstream AD markers...
February 1, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28153054/interaction-between-personality-traits-and-cerebrospinal-fluid-biomarkers-of-alzheimer-s-disease-pathology-modulates-cognitive-performance
#20
Domilė Tautvydaitė, Deepti Kukreja, Jean-Philippe Antonietti, Hugues Henry, Armin von Gunten, Julius Popp
BACKGROUND: During adulthood, personality characteristics may contribute to the individual capacity to compensate the impact of developing cerebral Alzheimer's disease (AD) pathology on cognitive impairment in later life. In this study we aimed to investigate whether and how premorbid personality traits interact with cerebrospinal fluid (CSF) markers of AD pathology to predict cognitive performance in subjects with mild cognitive impairment or mild AD dementia and in participants with normal cognition...
February 2, 2017: Alzheimer's Research & Therapy
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