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https://www.readbyqxmd.com/read/27911308/the-effects-of-gene-mutations-on%C3%A2-default%C3%A2-mode-network-in%C3%A2-familial%C3%A2-alzheimer-s-disease
#1
Xiaozhen Li, Eric Westman, Steinunn Thordardottir, Anne Kinhult Ståhlbom, Ove Almkvist, Kaj Blennow, Lars-Olof Wahlund, Caroline Graff
Familial Alzheimer's disease (FAD) mutations have very high penetrance but age at onset and rate of disease progression differ. Neuroimaging and cerebrospinal fluid (CSF) examinations in mutation carriers (MCs) may provide an opportunity to identify early biomarkers that can be used to track disease progression from presymptomatic to the dementia stages of disease. The default mode network (DMN) is a resting state neuronal network composed of regions known to associate with amyloid deposition in AD. We hypothesized that functional connectivity in the DMN might change at pre-clinical stages in FAD MCs and correlate with changes in CSF biomarkers as a consequence of AD brain pathology...
November 29, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911301/tau-platelets-correlate-with-regional-brain%C3%A2-atrophy-in-patients-with-alzheimer-s%C3%A2-disease
#2
Andrea Slachevsky, Leonardo Guzmán-Martínez, Carolina Delgado, Pablo Reyes, Gonzalo A Farías, Carlos Muñoz-Neira, Eduardo Bravo, Mauricio Farías, Patricia Flores, Cristian Garrido, James T Becker, Oscar L López, Ricardo B Maccioni
BACKGROUND: Intracellular neurofibrillary tangles are part of the core pathology of Alzheimer's disease (AD), which are mainly composed of hyperphosphorylated tau protein. OBJECTIVES: The purpose of this study is to determine whether high molecular weight (HMW) or low molecular weight (LMW) tau protein levels, as well as the ratio HMW/LMW, present in platelets correlates with brain magnetic resonance imaging (MRI) structural changes in normal and cognitively impaired subjects...
November 26, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911289/the-brain-s-structural-connectome-mediates-the-relationship-between-regional-neuroimaging-biomarkers-in%C3%A2-alzheimer-s-disease
#3
Sneha Pandya, Amy Kuceyeski, Ashish Raj
Alzheimer's disease (AD), one of the most common causes of dementia in adults, is a progressive neurodegenerative disorder exhibiting well-defined neuropathological hallmarks. It is known that disease pathology involves misfolded amyloid-β (Aβ) and tau proteins, and exhibits a relatively stereotyped progression over decades. The relationship between AD neuropathological hallmarks (Aβ, hypometabolism, and tau proteins) and imaging biomarkers (MRI, AV-45/FDG-PET) is not fully understood. In addition, biomarker pathologies are oftentimes discordant, wherein it may show varying levels of abnormality across brain regions...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27910888/microtubule-stabilising-peptides-rescue-tau-phenotypes-in-vivo
#4
Shmma Quraishe, Megan Sealey, Louise Cranfield, Amritpal Mudher
The microtubule cytoskeleton is a highly dynamic, filamentous network underpinning cellular structure and function. In Alzheimer's disease, the microtubule cytoskeleton is compromised, leading to neuronal dysfunction and eventually cell death. There are currently no disease-modifying therapies to slow down or halt disease progression. However, microtubule stabilisation is a promising therapeutic strategy that is being explored. We previously investigated the disease-modifying potential of a microtubule-stabilising peptide NAP (NAPVSIPQ) in a well-established Drosophila model of tauopathy characterised by microtubule breakdown and axonal transport deficits...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27909396/the-eye-as-a-biomarker-for-alzheimer-s-disease
#5
REVIEW
Jeremiah K H Lim, Qiao-Xin Li, Zheng He, Algis J Vingrys, Vickie H Y Wong, Nicolas Currier, Jamie Mullen, Bang V Bui, Christine T O Nguyen
Alzheimer's disease (AD) is a progressive neurodegenerative disorder resulting in dementia and eventual death. It is the leading cause of dementia and the number of cases are projected to rise in the next few decades. Pathological hallmarks of AD include the presence of hyperphosphorylated tau and amyloid protein deposition. Currently, these pathological biomarkers are detected either through cerebrospinal fluid analysis, brain imaging or post-mortem. Though effective, these methods are not widely available due to issues such as the difficulty in acquiring samples, lack of infrastructure or high cost...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27908726/activation-of-g-protein-coupled-estrogen-receptor-1-improves-early-onset-cognitive-impairment-via-pi3k-akt-pathway-in-rats-with-traumatic-brain-injury
#6
Ze-Fen Wang, Zhi-Yong Pan, Cheng-Shi Xu, Zhi-Qiang Li
Previous studies experimentally reveal that G-protein coupled estrogen receptor 1(GPER) has neuroprotection against ischemic injury. However, its effect on traumatic brain injury (TBI) is less well-established. Cognitive impairment following human TBI is a common clinical observation, and TBI is considered as a risk factor for Alzheimer's disease (AD). This study aimed to observe the possible protective effect of GPER on early-onset cognitive impairment after a single TBI and investigate the cellular mechanism underlying its actions...
November 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27906174/therapeutic-advantage-of-pro-electrophilic-drugs-to-activate-the-nrf2-are-pathway-in-alzheimer-s-disease-models
#7
Stuart A Lipton, Tayebeh Rezaie, Anthony Nutter, Kevin M Lopez, James Parker, Kunio Kosaka, Takumi Satoh, Scott R McKercher, Eliezer Masliah, Nobuki Nakanishi
Alzheimer's disease (AD) is characterized by synaptic and neuronal loss, which occurs at least partially through oxidative stress induced by oligomeric amyloid-β (Aβ)-peptide. Carnosic acid (CA), a chemical found in rosemary and sage, is a pro-electrophilic compound that is converted to its active form by oxidative stress. The active form stimulates the Keap1/Nrf2 transcriptional pathway and thus production of phase 2 antioxidant enzymes. We used both in vitro and in vivo models. For in vitro studies, we evaluated protective effects of CA on primary neurons exposed to oligomeric Aβ...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27905341/heidenhain-variant-of-creutzfeldt-jakob-disease-in-a-patient-who-had-bovine-bioprosthetic-valve-implantation
#8
Jehard Hashoul, Waleed Saliba, Irina Bloch, Haneen Jabaly-Habib
Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disorder characterized by rapidly progressing dementia, general neurologic deterioration, and death. When the leading symptoms are visual disturbances, it is termed as the Heidenhain variant of CJD (HvCJD). CJD was reported following prion-contaminated pericardium transplants but never after bovine bioprosthetic cardiac valve. In this case report, we describe HvCJD in a patient who had a bovine bioprosthetic cardiac valve implant. An 82-year-old-woman was referred to neuro-ophthalmology clinic for unexplained visual loss that started 1 month previously...
October 2016: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/27904486/neurofibrillary-tangles-in-alzheimer-s-disease-elucidation-of-the-molecular-mechanism-by-immunohistochemistry-and-tau-protein-phospho-proteomics
#9
Athanasios Metaxas, Stefan J Kempf
No abstract text is available yet for this article.
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27903811/%C3%AE-amyloid-in-csf-biomarker-for-preclinical-cerebral-amyloid-angiopathy
#10
Ellis S van Etten, Marcel M Verbeek, Jeroen van der Grond, Ronald Zielman, Sanneke van Rooden, Erik W van Zwet, Anna M van Opstal, Joost Haan, Steven M Greenberg, Mark A van Buchem, Marieke J H Wermer, Gisela M Terwindt
OBJECTIVE: To investigate CSF biomarkers in presymptomatic and symptomatic mutation carriers with hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D), a model for sporadic cerebral amyloid angiopathy, and to determine the earliest deposited form of β-amyloid (Aβ). METHODS: HCHWA-D mutation carriers and controls were enrolled in the cross-sectional EDAN (Early Diagnosis of Amyloid Angiopathy Network) study. The HCHWA-D group was divided into symptomatic carriers with a previous intracerebral hemorrhage and presymptomatic carriers...
November 30, 2016: Neurology
https://www.readbyqxmd.com/read/27902456/long-term-caloric-restriction-in-apoe-deficient-mice-results-in-neuroprotection-via-fgf21-induced-ampk-mtor-pathway
#11
Claire Rühlmann, Tjark Wölk, Tobias Blümel, Laura Stahn, Brigitte Vollmar, Angela Kuhla
Caloric restriction (CR) decelerates the aging process, extends lifespan and exerts neuroprotective effects in diverse species by so far unknown mechanisms. Based on known neuroprotective effects of fibroblastic growth factor 21 (Fgf21) we speculate that CR upregulates Fgf21, which phosphorylates neuronal AMP-activated protein kinase (AMPK), leading to a decrease of mammalian target of rapamycin (mTOR) signaling activity and an inhibition of tau-hyperphosphorylation. This in turn reduces the formation of neurofibrillary tangles, a neuropathological hallmark of Alzheimer´s disease...
November 29, 2016: Aging
https://www.readbyqxmd.com/read/27895577/fus1-ko-mouse-as-a-model-of-oxidative-stress-mediated-sporadic-alzheimer-s-disease-circadian-disruption-and-long-term-spatial-and-olfactory-memory-impairments
#12
Guillermo Coronas-Samano, Keeley L Baker, Winston J T Tan, Alla V Ivanova, Justus V Verhagen
Insufficient advances in the development of effective therapeutic treatments of sporadic Alzheimer's Disease (sAD) to date are largely due to the lack of sAD-relevant animal models. While the vast majority of models do recapitulate AD's hallmarks of plaques and tangles by virtue of tau and/or beta amyloid overexpression, these models do not reflect the fact that in sAD (unlike familial AD) these genes are not risk factors per se and that other mechanisms like oxidative stress, metabolic dysregulation and inflammation play key roles in AD etiology...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27893164/diagnostic-and-prognostic-value-of-human-prion-detection-in-cerebrospinal-fluid
#13
Aaron Foutz, Brian S Appleby, Clive Hamlin, Xiaoqin Liu, Sheng Yang, Yvonne Cohen, Wei Chen, Janis Blevins, Cameron Fausett, Han Wang, Pierluigi Gambetti, Shulin Zhang, Andrew Hughson, Curtis Tatsuoka, Lawrence B Schonberger, Mark L Cohen, Byron Caughey, Jiri G Safar
Objective-Several prion amplification systems have been proposed for detection of prions in cerebrospinal fluid (CSF), most recently, the measurements of prion seeding activity with second-generation real-time quaking-induced conversion (RT-QuIC). The objective of this study was to investigate the diagnostic performance of the RT-QuIC prion test in the broad phenotypic spectrum of prion diseases. Methods- We performed CSF RT-QuIC testing in 2,141 patients who had rapidly progressive neurological disorders, determined diagnostic sensitivity and specificity in 272 cases which were autopsied, and evaluated the impact of mutations and polymorphisms in the PRNP gene, and Type 1 or Type 2 of human prions on diagnostic performance...
November 28, 2016: Annals of Neurology
https://www.readbyqxmd.com/read/27890528/pathological-concentration-of-zinc-dramatically-accelerates-abnormal-aggregation-of-full-length-human-tau-and-thereby-significantly-increases-tau-toxicity-in-neuronal-cells
#14
Ji-Ying Hu, De-Lin Zhang, Xiao-Ling Liu, Xue-Shou Li, Xiao-Qing Cheng, Jie Chen, Hai-Ning Du, Yi Liang
A pathological hallmark of Alzheimer disease and other tauopathies is the formation of neurofibrillary tangles mainly composed of bundles of fibrils formed by microtubule-associated protein Tau. Here we study the effects of Zn(2+) on abnormal aggregation and cytotoxicity of a pathological mutant ΔK280 of full-length human Tau. As revealed by Congo red binding assays, transmission electron microscopy, immunofluorescence, Western blot, and immunogold electron microscopy, pathological concentration of Zn(2+) dramatically accelerates the fibrillization of ΔK280 both in vitro and in SH-SY5Y neuroblastoma cells...
November 23, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27890382/-alzheimer-s-disease-cerebro-spinal-fluid-biomarkers-a-clinical-research-tool-sometimes-useful-in-daily-clinical-practice-of-memory-clinics-for-the-diagnosis-of-complex-cases
#15
E Magnin, J Dumurgier, E Bouaziz-Amar, S Bombois, D Wallon, A Gabelle, S Lehmann, F Blanc, O Bousiges, D Hannequin, B Jung, C Miguet-Alfonsi, M Quillard, F Pasquier, K Peoc'h, J-L Laplanche, J Hugon, C Paquet
The role of biomarkers in clinical research was recently highlighted in the new criteria for the diagnosis of Alzheimer's disease. Cerebro-spinal fluid (CSF) biomarkers (total Tau protein, threonine 181 phosphorylated Tau protein and amyloid Aβ1-42 peptide) are associated with cerebral neuropathological lesions observed in Alzheimer's disease (neuronal death, neurofibrillary tangle with abnormal Tau deposits and amyloid plaque). Aβ1-40 amyloid peptide dosage helps to interpret Aβ1-42 results. As suggested in the latest international criteria and the French HAS (Haute Autorité de santé) recommendations, using theses CSF biomarkers should not be systematic but sometimes could be performed to improve confidence about the diagnostic of Alzheimer's disease in young subjects or in complex clinical situations...
November 24, 2016: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/27886009/diagnostic-accuracy-of-a-combined-analysis-of-cerebrospinal-fluid-t-prp-t-tau-p-tau-and-a%C3%AE-42-in-the-differential-diagnosis-of-creutzfeldt-jakob-disease-from-alzheimer-s-disease-with-emphasis-on-atypical-disease-variants
#16
Samir Abu Rumeileh, Francesca Lattanzio, Michelangelo Stanzani Maserati, Romana Rizzi, Sabina Capellari, Piero Parchi
According to recent studies, the determination of cerebrospinal fluid (CSF) total tau (t-tau)/phosphorylated tau (p-tau) ratio and total prion protein (t-PrP) levels significantly improves the accuracy of the diagnosis of Alzheimer's disease (AD) in atypical cases with clinical or laboratory features mimicking Creutzfeldt-Jakob disease (CJD). However, this has neither been validated nor tested in series including atypical CJD variants. Furthermore, the added diagnostic value of amyloid-β (Aβ)42 remains unclear...
November 19, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27884163/chronic-adiponectin-deficiency-leads-to-alzheimer-s-disease-like-cognitive-impairments-and-pathologies-through-ampk-inactivation-and-cerebral-insulin-resistance-in-aged-mice
#17
Roy Chun-Laam Ng, On-Yin Cheng, Min Jian, Jason Shing-Cheong Kwan, Philip Wing-Lok Ho, Kenneth King-Yip Cheng, Patrick Ka Kit Yeung, Lena Lei Zhou, Ruby Lai-Chong Hoo, Sookja Kim Chung, Aimin Xu, Karen Siu-Ling Lam, Koon Ho Chan
BACKGROUND: Insulin resistance is the major pathogenesis underlying type 2 diabetes mellitus (T2DM) and these patients have doubled risk of Alzheimer's disease (AD). Increasing evidence suggests that insulin resistance plays an important role in AD pathogenesis, possibly due to abnormal GSK3β activation, causing intra- and extracellular amyloid-beta (Aβ) accumulation. Adiponectin (APN) is an adipokine with insulin-sensitizing and anti-inflammatory effects. Reduced circulatory APN level is associated with insulin resistance and T2DM...
November 25, 2016: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/27884064/amyloid-fibril-proteins-and-amyloidosis-chemical-identification-and-clinical-classification-international-society-of-amyloidosis-2016-nomenclature-guidelines
#18
Jean D Sipe, Merrill D Benson, Joel N Buxbaum, Shu-Ichi Ikeda, Giampaolo Merlini, Maria J M Saraiva, Per Westermark
The Nomenclature Committee of the International Society of Amyloidosis (ISA) met during the XVth Symposium of the Society, 3 July-7 July 2016, Uppsala, Sweden, to assess and formulate recommendations for nomenclature for amyloid fibril proteins and the clinical classification of the amyloidoses. An amyloid fibril must exhibit affinity for Congo red and with green, yellow or orange birefringence when the Congo red-stained deposits are viewed with polarized light. While congophilia and birefringence remain the gold standard for demonstration of amyloid deposits, new staining and imaging techniques are proving useful...
December 2016: Amyloid: the International Journal of Experimental and Clinical Investigation
https://www.readbyqxmd.com/read/27883225/computational-screening-and-exploration-of-disease-associated-genes-in-alzheimer-s-disease
#19
Salma Jamal, Sukriti Goyal, Asheesh Shanker, Abhinav Grover
Alzheimer's is a neurodegenerative disease affecting large populations worldwide characterized mainly by progressive loss of memory along with various other symptoms. The foremost cause of the disease is still unclear, however various mechanisms have been proposed to cause the disease that include amyloid hypothesis, tau hypothesis and cholinergic hypothesis in addition to genetic factors. Various genes have been known to be involved which are APOE, PSEN1, PSEN2 and APP among others. In the present study, we have used computational methods to examine the pathogenic effects of non-synonymous single nucleotide polymorphisms (SNPs) associated with ABCA7, CR1, MS4A6A, CD2AP, PSEN1, PSEN2 and APP genes...
November 24, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27879670/the-protective-effects-of-icariin-against-the-homocysteine-induced-neurotoxicity-in-the-primary-embryonic-cultures-of-rat-cortical-neurons
#20
Xiao-Ang Li, Yuen-Shan Ho, Lei Chen, W L Wendy Hsiao
Icariin, an ingredient in the medicinal herb Epimedium brevicornum Maxim (EbM), has been considered as a potential therapeutic agent for neurodegenerative diseases such as Alzheimer's disease (AD). Hyperhomocysteinaemia is a risk factor for AD and other associated neurological diseases. In this study we aim to investigate whether icariin can reverse homocysteine (Hcy)-induced neurotoxicity in primary embryonic cultures of rat cortical neurons. Our findings demonstrated that icariin might be able restore the cytoskeleton network damaged by Hcy through the modulation of acetyl-α-tubulin, tyrosinated-α-tubulin, and phosphorylation of the tubulin-binding protein Tau...
November 22, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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