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https://www.readbyqxmd.com/read/28447221/deleterious-abca7-mutations-and-transcript-rescue-mechanisms-in-early-onset-alzheimer-s-disease
#1
Arne De Roeck, Tobi Van den Bossche, Julie van der Zee, Jan Verheijen, Wouter De Coster, Jasper Van Dongen, Lubina Dillen, Yalda Baradaran-Heravi, Bavo Heeman, Raquel Sanchez-Valle, Albert Lladó, Benedetta Nacmias, Sandro Sorbi, Ellen Gelpi, Oriol Grau-Rivera, Estrella Gómez-Tortosa, Pau Pastor, Sara Ortega-Cubero, Maria A Pastor, Caroline Graff, Håkan Thonberg, Luisa Benussi, Roberta Ghidoni, Giuliano Binetti, Alexandre de Mendonça, Madalena Martins, Barbara Borroni, Alessandro Padovani, Maria Rosário Almeida, Isabel Santana, Janine Diehl-Schmid, Panagiotis Alexopoulos, Jordi Clarimon, Alberto Lleó, Juan Fortea, Magda Tsolaki, Maria Koutroumani, Radoslav Matěj, Zdenek Rohan, Peter De Deyn, Sebastiaan Engelborghs, Patrick Cras, Christine Van Broeckhoven, Kristel Sleegers
Premature termination codon (PTC) mutations in the ATP-Binding Cassette, Sub-Family A, Member 7 gene (ABCA7) have recently been identified as intermediate-to-high penetrant risk factor for late-onset Alzheimer's disease (LOAD). High variability, however, is observed in downstream ABCA7 mRNA and protein expression, disease penetrance, and onset age, indicative of unknown modifying factors. Here, we investigated the prevalence and disease penetrance of ABCA7 PTC mutations in a large early onset AD (EOAD)-control cohort, and examined the effect on transcript level with comprehensive third-generation long-read sequencing...
April 27, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28444635/the-leukocentric-theory-of-neurological-disorder-a-manifesto
#2
Robert Fern
Approximately half of the human brain is composed of white matter (WM), a specialized tissue housing the axonal projection of neurons and their necessary supporting glial cells. Axons course long distances from their parent soma, have a delicate structure, large surface area and in many cases are dependent upon a uniquely close morphological arrangement with myelinating oligodendrocyte partners; all factors that may predispose them to injury and disease. WM damage is central to a range of well-characterized disorders including multiple sclerosis and spinal cord injury and is also makes a significant contribution to disorders often considered to be largely focused in gray matter; for example, in stroke where ~49% of injury by volume is located in WM...
April 25, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28443019/increased-diagnostic-accuracy-of-digital-vs-conventional-clock-drawing-test-for-discrimination-of-patients-in-the-early-course-of-alzheimer-s-disease-from-cognitively-healthy-individuals
#3
Stephan Müller, Oliver Preische, Petra Heymann, Ulrich Elbing, Christoph Laske
The conventional Clock Drawing Test (cCDT) is a rapid and inexpensive screening tool for detection of moderate and severe dementia. However, its usage is limited due to poor diagnostic accuracy especially in patients with mild cognitive impairment (MCI). The diagnostic value of a newly developed digital Clock Drawing Test (dCDT) was evaluated and compared with the cCDT in 20 patients with early dementia due to AD (eDAT), 30 patients with amnestic MCI (aMCI) and 20 cognitively healthy controls (HCs). Parameters assessed by dCDT were time while transitioning the stylus from one stroke to the next above the surface (i...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28441414/regional-early-and-progressive-loss-of-brain-pericytes-but-not-vascular-smooth-muscle-cells-in-adult-mice-with-disrupted-platelet-derived-growth-factor-receptor-%C3%AE-signaling
#4
Angeliki Maria Nikolakopoulou, Zhen Zhao, Axel Montagne, Berislav V Zlokovic
Pericytes regulate key neurovascular functions of the brain. Studies in pericyte-deficient transgenic mice with aberrant signaling between endothelial-derived platelet-derived growth factor BB (PDGF-BB) and platelet-derived growth factor receptor β (PDGFRβ) in pericytes have contributed to better understanding of the role of pericytes in the brain. Here, we studied PdgfrβF7/F7 mice, which carry seven point mutations that disrupt PDGFRβ signaling causing loss of pericytes and vascular smooth muscle cells (VSMCs) in the developing brain...
2017: PloS One
https://www.readbyqxmd.com/read/28440221/nptx2-and-cognitive-dysfunction-in-alzheimer-s-disease
#5
Mei-Fang Xiao, Desheng Xu, Michael T Craig, Kenneth A Pelkey, Chun-Che Chien, Yang Shi, Juhong Zhang, Susan Resnick, Olga Pletnikova, David Salmon, James Brewer, Steven Edland, Jerzy Wegiel, Benjamin Tycko, Alena Savonenko, Roger H Reeves, Juan C Troncoso, Chris J McBain, Douglas Galasko, Paul F Worley
Memory loss in Alzheimer's disease (AD) is attributed to pervasive weakening and loss of synapses. Here, we present findings supporting a special role for excitatory synapses connecting pyramidal neurons of the hippocampus and cortex with fast-spiking parvalbumin (PV) interneurons that control network excitability and rhythmicity. Excitatory synapses on PV interneurons are dependent on the AMPA receptor subunit GluA4, which is regulated by presynaptic expression of the synaptogenic immediate early gene NPTX2 by pyramidal neurons...
March 23, 2017: ELife
https://www.readbyqxmd.com/read/28438696/altered-temporal-lobe-white-matter-lipid-ion-profiles-in-an-experimental-model-of-sporadic-alzheimer-s-disease
#6
Ming Tong, Raiane Leão, Gina V Vimbela, Emine B Yalcin, Jared Kay, Alexander Krotow, Suzanne M de la Monte
BACKGROUND: White matter is an early and important yet under-evaluated target of Alzheimer's disease (AD). Metabolic impairments due to insulin and insulin-like growth factor resistance contribute to white matter degeneration because corresponding signal transduction pathways maintain oligodendrocyte function and survival. METHODS: This study utilized a model of sporadic AD in which adult Long Evans rats administered intracerebral streptozotocin (i.c. STZ) developed AD-type neurodegeneration...
April 21, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28438484/simultaneous-object-perception-deficits-are-related-to-reduced-visual-processing-speed-in-amnestic-mild-cognitive-impairment
#7
Adriana L Ruiz-Rizzo, Peter Bublak, Petra Redel, Timo Grimmer, Hermann J Müller, Christian Sorg, Kathrin Finke
Simultanagnosia, an impairment in simultaneous object perception, has been attributed to deficits in visual attention and, specifically, to processing speed. Increasing visual attention deficits manifest over the course of Alzheimer's disease (AD), where the first changes are present already in its symptomatic predementia phase: amnestic mild cognitive impairment (aMCI). In this study, we examined whether patients with aMCI due to AD show simultaneous object perception deficits and whether and how these deficits relate to visual attention...
April 4, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28436390/biomarkers-for-early-diagnosis-of%C3%A2-alzheimer-s-disease-in-the-oldest-old-yes-or-no
#8
Lucia Paolacci, David Giannandrea, Patrizia Mecocci, Lucilla Parnetti
In recent years, many efforts have been spent to identify sensitive biomarkers able to improve the accuracy of Alzheimer's disease (AD) diagnosis. Two different workgroups (NIA-AA and IWG) included cerebrospinal fluid (CSF) and neuroimaging findings in their sets of criteria in order to improve diagnostic accuracy as well as early diagnosis. The number of subjects with cognitive impairment increases with aging but the oldest old (≥85 years of age), the fastest growing age group, is still the most unknown from a biological point of view...
April 15, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28436389/ethical-considerations-for-deep-brain-stimulation-trials-in-patients-with-early-onset-alzheimer-s-disease
#9
John Noel M Viaña, Merlin Bittlinger, Frederic Gilbert
Several studies of deep brain stimulation (DBS) of the fornix or the nucleus basalis of Meynert have been recently conducted in people with Alzheimer's disease, with several recruiting participants <65 and thus have early-onset Alzheimer's disease (EOAD). Although EOAD accounts for less than 5.5% of AD cases, ethical considerations must still be made when performing DBS trials including these participants since a portion of people with EOAD, especially those possessing autosomal-dominant mutations, have an atypical and more aggressive disease progression...
April 15, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28435465/hypertension-cerebrovascular-impairment-and-cognitive-decline-in-aged-a%C3%AE-pp-ps1-mice
#10
Maximilian Wiesmann, Valerio Zerbi, Diane Jansen, Dieter Lütjohann, Andor Veltien, Arend Heerschap, Amanda J Kiliaan
Cardiovascular risk factors, especially hypertension, are also major risk factors for Alzheimer's disease (AD). To elucidate the underlying vascular origin of neurodegenerative processes in AD, we investigated the relation between systolic blood pressure (SBP) cerebral blood flow (CBF) and vasoreactivity with brain structure and function in a 16-18 months old double transgenic AβPPswe/PS1dE9 (AβPP/PS1) mouse model for AD. These aging AβPP/PS1 mice showed an increased SBP linked to a declined regional CBF...
2017: Theranostics
https://www.readbyqxmd.com/read/28434708/dual-phase-18-f-florbetapir-positron-emission-tomography-in-patients-with-primary-progressive-aphasia-alzheimer-s-disease-and-healthy-controls-a-preliminary-study
#11
Hung-Chou Kuo, Ing-Tsung Hsiao, Chia-Ju Hsieh, Chu-Yun Huang, Kuo-Lun Huang, Yau-Yau Wai, Wen-Li Chuang, Mei-Ping Kung, Yi-Chuan Chu, Tzu-Chen Yen, Kun-Ju Lin, Chin-Chang Huang
BACKGROUND: To determine whether dual-phase (18)F-florbetapir positron emission tomography imaging with perfusion-like and amyloid deposition information can distinguish among primary progressive aphasia (PPA), Alzheimer's disease (AD), and healthy controls (HCs). METHODS: Patients diagnosed with PPA, including four semantic dementia (SD) and two progressive nonfluent aphasia (PNFA), as well as one logopenic variant (LV) of PPA, were studied. All PPA patients, and age-/sex-matched patients with probable AD (n=8) and HCs (n=8) were subjected to dual-phase (18)F-florbetapir imaging...
April 20, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28434692/immune-hyperreactivity-of-a%C3%AE-plaque-associated-microglia-in-alzheimer-s-disease
#12
Zhuoran Yin, Divya Raj, Nasrin Saiepour, Debby Van Dam, Nieske Brouwer, Inge R Holtman, Bart J L Eggen, Thomas Möller, Joseph A Tamm, Aicha Abdourahman, Elly M Hol, Willem Kamphuis, Thomas A Bayer, Peter P De Deyn, Erik Boddeke
Alzheimer's disease (AD) is strongly associated with microglia-induced neuroinflammation. Particularly, Aβ plaque-associated microglia take on an "activated" morphology. However, the function and phenotype of these Aβ plaque-associated microglia are not well understood. We show hyperreactivity of Aβ plaque-associated microglia upon systemic inflammation in transgenic AD mouse models (i.e., 5XFAD and APP23). Gene expression profiling of Aβ plaque-associated microglia (major histocompatibility complex II(+) microglia) isolated from 5XFAD mice revealed a proinflammatory phenotype...
March 27, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28434642/-late-life-depression-or-prodromal-alzheimer-s-disease-which-tools-for-the-differential-diagnosis
#13
A-I Gasser, V Salamin, S Zumbach
INTRODUCTION: Depression and Alzheimer's disease are both very frequent in elderly people. Cognitive deficits are the hallmark of Alzheimer's disease, but they are also common in depressed elderly people who often present cognitive deficits such as memory, attention and executive function problems. On the other hand, people with early Alzheimer's disease demonstrate emotional and behavioral disorders generally encountered in depression such as loss of energy, apathy, mood disorder, and irritability...
April 20, 2017: L'Encéphale
https://www.readbyqxmd.com/read/28433649/chronic-nicotine-attenuates-behavioral-and-synaptic-plasticity-impairments-in-a-streptozotocin-model-of-alzheimer-s-disease
#14
Esteves Im, Lopes-Aguiar C, Rossignoli Mt, Ruggiero Rn, Broggini Acs, Bueno-Junior Ls, Kandratavicius L, Monteiro Mr, Romcy-Pereira Rn, Leite Jp
Brain glucose metabolism is altered in sporadic Alzheimer's disease (sAD), whose pathologies are reproduced in rodents by intracerebroventricular (icv) infusion of streptozotocin (STZ) in subdiabetogenic doses. The icv-STZ model also culminates in central cholinergic dysfunctions, which in turn are known to underlie both the sAD cognitive decline, and synaptic plasticity impairments. Considering the cognitive-enhancing potential of chronic nicotine (Nic), we investigated whether it attenuates icv-STZ-induced impairments in recognition memory and synaptic plasticity in a cognition-relevant substrate: the hippocampal CA1-medial prefrontal cortex (mPFC) pathway...
April 19, 2017: Neuroscience
https://www.readbyqxmd.com/read/28433262/primary-motor-cortex-alterations-in-alzheimer-disease-a-study-in-the-3xtg-ad-model
#15
E Orta-Salazar, A I Feria-Velasco, S Díaz-Cintra
INTRODUCTION: In humans and animal models, Alzheimer disease (AD) is characterised by accumulation of amyloid-β peptide (Aβ) and hyperphosphorylated tau protein, neuronal degeneration, and astrocytic gliosis, especially in vulnerable brain regions (hippocampus and cortex). These alterations are associated with cognitive impairment (loss of memory) and non-cognitive impairment (motor impairment). The purpose of this study was to identify cell changes (neurons and glial cells) and aggregation of Aβ and hyperphosphorylated tau protein in the primary motor cortex (M1) in 3xTg-AD mouse models at an intermediate stage of AD...
April 19, 2017: Neurología: Publicación Oficial de la Sociedad Española de Neurología
https://www.readbyqxmd.com/read/28432138/inhibition-of-drp1-ameliorates-synaptic-depression-a%C3%AE-deposition-and-cognitive-impairment-in-alzheimer-s-disease-model
#16
Seung-Hyun Baek, So Jung Park, Jae In Jeong, Sung Hyun Kim, Jihoon Han, Jae Won Kyung, Sang-Ha Baik, Yuri Choi, Bo-Youn Choi, Jinsu Park, Gahee Bahn, Ji Hyun Shin, Doo Sin Jo, Joo-Yong Lee, Choon-Gon Jang, Thiruma V Arumugam, Jongpil Kim, Jeung-Whan Han, Jae-Young Koh, Dong-Hyung Cho, Dong-Gyu Jo
Excessive mitochondrial fission is a prominent early event, and contributes to mitochondrial dysfunction, synaptic failure and neuronal cell death in the progression of Alzheimer's disease (AD). However, it remains to be determined whether inhibition of excessive mitochondrial fission is beneficial in mammal models of AD. To determine whether dynamin-related protein 1 (Drp1), a key regulator of mitochondrial fragmentation, can be a disease-modifying therapeutic target for AD, we examine the effects of Drp1 inhibitor on mitochondrial and synaptic dysfunctions induced by oligomeric β-amyloid (Aβ) in neurons, and neuropathology and cognitive functions in APP/PS1 double transgenic AD mice...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28431735/characterization-of-an-amyloid-only-transgenic-b6c3-tg-appswe-psen1de9-85dbo-mmjax-mouse-model-of-alzheimer-s-disease
#17
G S Finnie, R Gunnarsson, J Manavis, P C Blumbergs, K A Mander, S Edwards, C Van den Heuvel, J W Finnie
The spatiotemporal pattern of cerebral amyloid deposition, detectable as light microscopically recognizable aggregates in an 'amyloid only' transgenic mouse model of Alzheimer's disease, B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax, is reported for the first time in this strain. Monoclonal and polyclonal antibodies were used to detect amyloid deposition immunohistochemically in brains collected from these mice at 3-12 months of age. Amyloid aggregates (20-200 μm) were first found in serial, whole coronal sections of brain at 4 months of age and these increased progressively, plateauing at 11-12 months...
April 18, 2017: Journal of Comparative Pathology
https://www.readbyqxmd.com/read/28431620/role-of-inflammatory-molecules-in-the-alzheimer-s-disease-progression-and-diagnosis
#18
REVIEW
Eva Bagyinszky, Vo Van Giau, Kyuhwan Shim, Kyoungho Suk, Seong Soo A An, SangYun Kim
Alzheimer's disease (AD) is a complex disorder and the most common form of neurodegenerative dementia. Several genetic, environmental, and physiological factors, including inflammations and metabolic influences, are involved in the progression of AD. Inflammations are composed of complicated networks of many chemokines and cytokines with diverse cells. Inflammatory molecules are needed for the protection against pathogens, and maintaining their balances is important for normal physiological function. Recent studies demonstrated that inflammation may be involved in neurodegenerative dementia...
May 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28431511/validation-of-the-short-version-of-the-10-66-dementia-diagnosis-in-multiethnic-asian-older-adults-in-singapore
#19
Edimansyah Abdin, Janhavi Ajit Vaingankar, Louisa Picco, Boon Yiang Chua, Martin Prince, Siow Ann Chong, Mythily Subramaniam
BACKGROUND: To validate the short version of the 10/66 dementia diagnosis against the standard version of the 10/66 dementia diagnosis and clinical diagnosis and examine concurrent validity with the World Health Organisation Disability Assessment schedule and care needs in a multiethnic Asian older adult population in Singapore. METHODS: Data from the Well-being of the Singapore Elderly study, a nationally representative survey of the older Singapore Resident population aged 60 years and above was used...
April 21, 2017: BMC Geriatrics
https://www.readbyqxmd.com/read/28428473/technical-considerations-on-scanning-and-image-analysis-for-amyloid-pet-in-dementia
#20
Go Akamatsu, Akihito Ohnishi, Kazuki Aita, Yasuhiko Ikari, Yasuji Yamamoto, Michio Senda
Brain imaging techniques, such as computed tomography (CT), magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET), can provide essential and objective information for the early and differential diagnosis of dementia. Amyloid PET is especially useful to evaluate the amyloid-β pathological process as a biomarker of Alzheimer's disease. This article reviews critical points about technical considerations on the scanning and image analysis methods for amyloid PET...
2017: Nihon Hoshasen Gijutsu Gakkai Zasshi
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