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Journal of Alzheimer's Disease: JAD

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https://www.readbyqxmd.com/read/28059798/sporadic-cases-with-novel-mutations-and-pedigree-in-hereditary-leukoencephalopathy-with-axonal-spheroids
#1
Liyong Wu, Jia Liu, Longze Sha, Xianling Wang, Jieying Li, Jing Dong, Jianping Jia
Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal dominant hereditary disease, featured by cerebral white matter degeneration with demyelination and axonal spheroids. We collected three gene-confirmed HDLS cases in our neurodegenerative clinic. Two HDLS cases were sporadic with novel mutations, while another case had a family history with previously described mutations. All three cases suffered memory problems with white matter lesions and pyramid signs. No obvious clinical differences were observed between sporadic and familial HDLS cases...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28059797/effect-of-spinal-manometers-on-cerebrospinal-fluid-amyloid-%C3%AE-concentration
#2
Jamie Toombs, Martha S Foiani, Ross W Paterson, Amanda Heslegrave, Selina Wray, Jonathan M Schott, Nick C Fox, Michael P Lunn, Kaj Blennow, Henrik Zetterberg
The effect of spinal manometers on cerebrospinal fluid (CSF) amyloid-β (Aβ) concentration was investigated. Pooled human CSF samples were divided in two, one half passed through a manometer into a collection tube, the other transferred directly to a collection tube. CSF was analyzed for Aβ38/40/42 using an electrochemiluminescence immunoassay. Relative to control, use of a manometer decreased Aβ38/40/42 concentration by 5.6% (±1.5SE), 4.4% (±1.7SE), and 4.3% (±2.4SE), respectively. The ratios of Aβ42 :40, Aβ42 :38, and Aβ40 :38 were not affected by manometer treatment...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28059796/a-common-variant-in-the-mc1r-gene-p-v92m-is-associated-with-alzheimer-s-disease-risk
#3
Gemma Tell-Marti, Joan Anton Puig-Butille, Miriam Potrony, Estel Plana, Celia Badenas, Anna Antonell, Raquel Sanchez-Valle, José L Molinuevo, Alberto Lleó, Daniel Alcolea, Juan Fortea, Ruben Fernandez-Santiago, Jordi Clarimón, Albert Lladó, Susana Puig
Despite the recent identification of some novel risk genes for Alzheimer's disease (AD), the genetic etiology of late-onset Alzheimer's disease (LOAD) remains largely unknown. The inclusion of these novel risk genes to the risk attributable to the APOE gene accounts for roughly half of the total genetic variance in LOAD. The evidence indicates that undiscovered genetic factors may contribute to AD susceptibility. In the present study, we sequenced the MC1R gene in 525 Spanish LOAD patients and in 160 controls...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28059795/evidence-of-a-cardiovascular-function-for-microtubule-associated-protein-tau
#4
Ashenafi H Betrie, Scott Ayton, Ashley I Bush, James A Angus, Peng Lei, Christine E Wright
Aggregation of tau protein into intracellular deposits is a pathognomonic feature of tauopathies such as Alzheimer's disease (AD) and lowering tau is a prominent therapeutic strategy under development. However, the physiological function of tau protein is not well known, particularly in the periphery. Lowering tau protein risks disrupting its physiological role leading to unwanted effects. In this study, the presence of tau protein in cardiac tissue is confirmed and the functional role in the cardiovascular system and the consequences of its loss were explored...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28059794/oxidative-stress-synaptic-dysfunction-and%C3%A2-alzheimer-s-disease
#5
Eric Tönnies, Eugenia Trushina
Alzheimer's disease (AD) is a devastating neurodegenerative disorder without a cure. Most AD cases are sporadic where age represents the greatest risk factor. Lack of understanding of the disease mechanism hinders the development of efficacious therapeutic approaches. The loss of synapses in the affected brain regions correlates best with cognitive impairment in AD patients and has been considered as the early mechanism that precedes neuronal loss. Oxidative stress has been recognized as a contributing factor in aging and in the progression of multiple neurodegenerative diseases including AD...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28059793/resveratrol-intervenes-in-the-cholesterol-and-isoprenoid-mediated-amyloidogenic-processing-of-a%C3%AE-pp-in-familial-alzheimer-s-disease
#6
Mohan Sathya, Ponnusamy Moorthi, Palanisamy Premkumar, Mahesh Kandasamy, Kesavan Swaminathan Jayachandran, Muthuswamy Anusuyadevi
Deterioration of cholesterol metabolism has recently been a frontier subject of investigation in the field of Alzheimer's disease (AD). Though amyloid-β protein precursor (AβPP) primes the pathological cascade, changes in cholesterol levels and its intermediates, geranyl geranyl pyrophosphate and farnesyl pyrophosphate, is expected to have a different consequence on AβPP processing and amyloid-β (Aβ) generation. However, the use of statins (HMG-COA reductase inhibitor) has been widely implicated in slowing down the pathogenic progression of AD, while the epidemiological reports on its biological effect remains controversial...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28059792/quantitative-comparison-of-dense-core-amyloid-plaque-accumulation-in-amyloid-%C3%AE-protein-precursor-transgenic-mice
#7
Peng Liu, John H Reichl, Eshaan R Rao, Brittany M McNellis, Eric S Huang, Laura S Hemmy, Colleen L Forster, Michael A Kuskowski, David R Borchelt, Robert Vassar, Karen H Ashe, Kathleen R Zahs
There exist several dozen lines of transgenic mice that express human amyloid-β protein precursor (AβPP) with Alzheimer's disease (AD)-linked mutations. AβPP transgenic mouse lines differ in the types and amounts of Aβ that they generate and in their spatiotemporal patterns of expression of Aβ assemblies, providing a toolkit to study Aβ amyloidosis and the influence of Aβ aggregation on brain function. More complete quantitative descriptions of the types of Aβ assemblies present in transgenic mice and in humans during disease progression should add to our understanding of how Aβ toxicity in mice relates to the pathogenesis of AD...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28059791/mitochondrial-repair-effects-of-oxygen-treatment-on-alzheimer-s-disease-model-mice-revealed-by-quantitative-proteomics
#8
Hao Wang, Xiaoyu Hong, Yong Wang
Mitochondrial dysfunction plays a pivotal role in Alzheimer's disease (AD), even before signs of AD pathology are evident. Our previous research has shown that oxygen treatment can improve cognitive function in AD model mice. To address whether oxygen treatment is beneficial to mitochondrial biology, we analyzed differential expressions of hippocampal mitochondrial proteins in AD model mice given supplementary oxygen. Numerous respiratory chain, Kreb's cycle, and glycolysis proteins were upregulated significantly after oxygen treatment, suggesting that oxygen therapy can alleviate mitochondrial damage...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28059790/combined-creutzfeldt-jakob-jacob-alzheimer-s-disease-cases-are-important-in-search-for-microbes-in-alzheimer-s-disease
#9
Frank O Bastian
The question whether Alzheimer's disease is infectious as brought up in the recent editorial published in the Journal of Alzheimer's Disease is complicated by the controversy whether the causal agent is a microbe or a misfolded host protein (amyloid). The replicating amyloid (prion) theory, based upon data from studies of Creutzfeldt-Jakob disease (CJD) and other transmissible spongiform encephalopathies (TSEs), has been challenged since the prion can be separated from TSE infectivity, and spiroplasma, a wall-less bacterium, has been shown to be involved in the pathogenesis of CJD...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28059789/the-mild-behavioral-impairment-checklist%C3%A2-mbi-c-a-rating-scale-for%C3%A2-neuropsychiatric-symptoms-in%C3%A2-pre-dementia-populations
#10
Zahinoor Ismail, Luis Agüera-Ortiz, Henry Brodaty, Alicja Cieslak, Jeffrey Cummings, Corinne E Fischer, Serge Gauthier, Yonas E Geda, Nathan Herrmann, Jamila Kanji, Krista L Lanctôt, David S Miller, Moyra E Mortby, Chiadi U Onyike, Paul B Rosenberg, Eric E Smith, Gwenn S Smith, David L Sultzer, Constantine Lyketsos
BACKGROUND: Mild behavioral impairment (MBI) is a construct that describes the emergence at ≥50 years of age of sustained and impactful neuropsychiatric symptoms (NPS), as a precursor to cognitive decline and dementia. MBI describes NPS of any severity, which are not captured by traditional psychiatric nosology, persist for at least 6 months, and occur in advance of or in concert with mild cognitive impairment. While the detection and description of MBI has been operationalized in the International Society to Advance Alzheimer's Research and Treatment - Alzheimer's Association (ISTAART-AA) research diagnostic criteria, there is no instrument that accurately reflects MBI as described...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28059788/silicic-acid-and-beer-consumption-reverses-the-metal-imbalance-and%C3%A2-the%C3%A2-prooxidant-status-induced-by%C3%A2-aluminum-nitrate-in-mouse-brain
#11
María José González-Muñoz, Alba Garcimartán, Isabel Meseguer, Carmen José Mateos-Vega, José María Orellana, Antonio Peña-Fernández, Juana Benedí, Francisco J Sánchez-Muniz
BACKGROUND: Emerging evidence suggests that by affecting mineral balance, aluminum (Al) may enhance some events associated with neurodegenerative diseases. AIM: To examine the effect of Al(NO3)3 exposure on brain Al, cooper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), silicon (Si), and zinc (Zn) levels, and the metal-change implication in brain oxidant and inflammatory status. METHODS: Four groups of six-week-old male NMRI mice were treated for three months: i) controls, administrated with deionized water; ii) Al, which received Al(NO3)3; iii) Al+silicic acid, which were given Al(NO3)3 plus silicic acid; and iv) Al+beer, which received Al(NO3)3 plus beer...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28059787/neurons-derived-from-induced-pluripotent-stem-cells-of-patients-with-down-syndrome-reproduce-early-stages-of-alzheimer-s-disease-type-pathology-in-vitro
#12
Erdem B Dashinimaev, Alexander S Artyuhov, Alexey P Bolshakov, Ekaterina A Vorotelyak, Andrey V Vasiliev
People with Down syndrome (DS) are at high risk of developing pathology similar to Alzheimer's disease (AD). Modeling of this pathology in vitro may be useful for studying this phenomenon. In this study, we analyzed three different cultures of neural cells carrying trisomy of chromosome 21, which were generated by directed differentiation from induced pluripotent stem cells (iPS cells). We report here that in vitro generated DS neural cells have abnormal metabolism of amyloid-β (Aβ) manifested by increased secretion and accumulation of Aβ granules of Aβ42 pathological isoform with upregulated expression of the APP gene...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28059786/death-of-dementia-patients-in-psychiatric-hospitals-and-regional-supply-of-psychiatric-services-study-of-the-national-data-from-1996-to-2014-in-japan
#13
Miharu Nakanishi, Junko Niimura, Syudo Yamasaki, Atsushi Nishida
BACKGROUND: Japan designates psychiatric inpatient care for behavior management of individuals with dementia and for helping dementia patients discharge to home. However, there has been no examination of the effectiveness of this strategy. OBJECTIVE: The present study investigated the association between dementia and the discharge destination of patients in psychiatric hospitals. METHODS: Data from the National Patient Survey, which is a nationally representative cross-sectional survey of inpatient care, were used...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28059785/amylin-enhances-amyloid-%C3%AE-peptide-brain-to-blood-efflux-across-the-blood-brain-barrier
#14
Loqman A Mohamed, Haihao Zhu, Youssef M Mousa, Erming Wang, Wei Qiao Qiu, Amal Kaddoumi
Findings from Alzheimer's disease (AD) mouse models showed that amylin treatment improved AD pathology and enhanced amyloid-β (Aβ) brain to blood clearance; however, the mechanism was not investigated. Using the Tg2576 AD mouse model, a single intraperitoneal injection of amylin significantly increased Aβ serum levels, and the effect was abolished by AC253, an amylin receptor antagonist, suggesting that amylin effect could be mediated by its receptor. Subsequent mechanistic studies showed amylin enhanced Aβ transport across a cell-based model of the blood-brain barrier (BBB), an effect that was abolished when the amylin receptor was inhibited by two amylin antagonists and by siRNA knockdown of amylin receptor Ramp3...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28059784/an-international-comparative-study-on%C3%A2-driving-regulations-on-people-with%C3%A2-dementia
#15
You Joung Kim, Hoyoung An, Binna Kim, Young Shin Park, Ki Woong Kim
Over 40% of people with dementia drive, with a two to five times greater accident risk than controls. This has fueled public concerns about the risk of traffic accidents by drivers with dementia (DWD). We compared driving regulations on seniors and DWD between ten European and Asia-Pacific countries to identify key implications for national strategies. Moderate to severe dementia was a reason for driver's license revocation in all countries. However, regulations on mild dementia varied considerably, with most basing their decisions on severity, rather than simply the presence of dementia...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28059783/improved-cerebrospinal-fluid-based-discrimination-between-alzheimer-s-disease-patients-and-controls-after-correction-for-ventricular-volumes
#16
Linda J C van Waalwijk van Doorn, Juan D Gispert, H Bea Kuiperij, Jurgen A H R Claassen, Andrea Arighi, Inês Baldeiras, Kaj Blennow, Marco Bozzali, Miguel Castelo-Branco, Enrica Cavedo, Derya D Emek-Savaş, Erden Eren, Paolo Eusebi, Lucia Farotti, Chiara Fenoglio, Juan Fortea Ormaechea, Yvonne Freund-Levi, Giovanni B Frisoni, Daniela Galimberti, Sermin Genc, Viviana Greco, Harald Hampel, Sanna-Kaisa Herukka, Yawu Liu, Albert Lladó, Alberto Lleó, Flavio M Nobili, Kader K Oguz, Lucilla Parnetti, João Pereira, Agnese Picco, Maria Pikkarainen, Catarina Resende de Oliveira, Esen Saka, Nicola Salvadori, Raquel Sanchez-Valle, Isabel Santana, Elio Scarpini, Philip Scheltens, Hilkka Soininen, Roberto Tarducci, Charlotte Teunissen, Magda Tsolaki, Andrea Urbani, Eduard Vilaplana Martinez, Pieter Jelle Visser, Asa K Wallin, Görsev Yener, José L Molinuevo, Olga Meulenbroek, Marcel M Verbeek
Cerebrospinal fluid (CSF) biomarkers may support the diagnosis of Alzheimer's disease (AD). We studied if the diagnostic power of AD CSF biomarker concentrations, i.e., Aβ42, total tau (t-tau), and phosphorylated tau (p-tau), is affected by differences in lateral ventricular volume (VV), using CSF biomarker data and magnetic resonance imaging (MRI) scans of 730 subjects, from 13 European Memory Clinics. We developed a Matlab-algorithm for standardized automated segmentation analysis of T1 weighted MRI scans in SPM8 for determining VV, and computed its ratio with total intracranial volume (TIV) as proxy for total CSF volume...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28059782/differential-hemispheric-predilection-of%C3%A2-microstructural-white-matter-and%C3%A2-functional-connectivity-abnormalities-between-respectively-semantic-and%C3%A2-behavioral-variant-frontotemporal-dementia
#17
Rozanna Meijboom, Rebecca M E Steketee, Leontine S Ham, Aad van der Lugt, John C van Swieten, Marion Smits
Semantic dementia (SD) and behavioral variant frontotemporal dementia (bvFTD), subtypes of frontotemporal dementia, are characterized by distinct clinical symptoms and neuroimaging features, with predominant left temporal grey matter (GM) atrophy in SD and bilateral or right frontal GM atrophy in bvFTD. Such differential hemispheric predilection may also be reflected by other neuroimaging features, such as brain connectivity. This study investigated white matter (WM) microstructure and functional connectivity differences between SD and bvFTD, focusing on the hemispheric predilection of these differences...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28035938/dementia-and-pressure-ulcers-is-there-a%C3%A2-close-pathophysiological-interrelation
#18
Efraim Jaul, Oded Meiron
The current theoretical investigation aimed to explore common pathophysiological mechanisms underlying dementia and pressure ulcers (PU). Along with the increased longevity, especially in frail elderly patients, there is a higher rate of functional and cognitive impairment with dementia coinciding with disabilities, immobility resulting in a higher rate of PU. Understanding common etiological paths resulting in pressure ulcers and dementia is likely to produce new treatment strategies that could lead to the prevention of comorbid complications...
December 30, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28035937/mtorc2-rictor-in-alzheimer-s-disease-and-reversal-of-amyloid-%C3%AE-expression-induced-insulin-resistance-and-toxicity-in-rat-primary-cortical-neurons
#19
Han-Kyu Lee, Bumsup Kwon, Cynthia A Lemere, Suzanne de la Monte, Kyohei Itamura, Austin Y Ha, Henry W Querfurth
Mammalian target of rapamycin complex 1 (mTORC1), a nutrient sensor and central controller of cell growth and proliferation, is altered in various models of Alzheimer's disease (AD). Even less studied or understood in AD is mammalian target of rapamycin complex 2 (mTORC2) that influences cellular metabolism, in part through the regulations of Akt/PKB and SGK. Dysregulation of insulin/PI3K/Akt signaling is another important feature of AD pathogenesis. We found that both total mTORC1 and C2 protein levels and individual C1 and C2 enzymatic activities were decreased in human AD brain samples...
December 30, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28035936/association-of-cancer-history-with-alzheimer-s-disease-dementia-and-neuropathology
#20
Mark Yarchoan, Bryan D James, Raj C Shah, Zoe Arvanitakis, Robert S Wilson, Julie Schneider, David A Bennett, Steven E Arnold
BACKGROUND: Cancer and Alzheimer's disease (AD) are common diseases of aging and share many risk factors. Surprisingly, however, epidemiologic data from several recent independent cohort studies suggest that there may be an inverse association between these diseases. OBJECTIVE: To determine the relationship between history of cancer and odds of dementia proximate to death and neuropathological indices of AD. METHODS: Using data from two separate clinical-pathologic cohort studies of aging and AD, the Religious Orders Study (ROS) and the Rush Memory and Aging Project (MAP), we compared odds of AD dementia proximate to death among participants with and without a history of cancer...
December 30, 2016: Journal of Alzheimer's Disease: JAD
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