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Pashtun Shahim, Kaj Blennow, Per Johansson, Johan Svensson, Simone Lista, Harald Hampel, Leif Christer Andersson, Henrik Zetterberg
Stanniocalcin-1 (STC-1) is a nerve cell-enriched protein involved in intracellular calcium homeostasis regulation. Changes in calcium regulation are hypothesized to play a role in the pathophysiology of Alzheimer's disease (AD). The expression of STC-1 increases in response to ischemic stroke, but whether it is altered in neurodegenerative disorder, particularly Alzheimer's disease (AD), has not been investigated before. We measured STC-1 in cerebrospinal fluid (CSF) samples from a total of 163 individuals including AD, prodromal AD (pAD), mixed AD, stable mild cognitive impairment (sMCI), and diagnoses of other dementia than AD, as well as cognitively normal controls (CNC) enrolled at academic centers in France and Sweden...
September 19, 2016: Neuromolecular Medicine
Daniela Scarabino, Elisabetta Broggio, Giuseppe Gambina, Carlotta Maida, Maria Rosa Gaudio, Rosa Maria Corbo
Mild cognitive impairment (MCI) is the transition stage between the normal aging process and dementia itself. The most common clinical phenotype is amnestic MCI (aMCI) [subtypes: single domain (sMCI) and multiple domains (mMCI)], which is considered prodromal to Alzheimer's disease (AD). The APOE (apolipoprotein E) e4 allele is the most important genetic risk factor for AD, but its association with MCI onset and conversion to AD is controversial. In this follow-up study of 88 aMCI patients (68% sMCI and 32% mMCI at baseline), we examined APOE genotypes and plasma levels in relation to MCI development and progression based on their clinical/cognitive data obtained at baseline and follow-up assessment (mean follow-up time = 6...
September 8, 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Tiantian Qiu, Xiao Luo, Zhujing Shen, Peiyu Huang, Xiaojun Xu, Jiong Zhou, Minming Zhang
Mild cognitive impairment (MCI) is a heterogeneous condition associated with a high risk of progressing to Alzheimer's disease (AD). Although functional brain network alterations have been observed in progressive MCI (pMCI), the underlying pathological mechanisms of network alterations remain unclear. In the present study, we evaluated neuropsychological, imaging, and cerebrospinal fluid (CSF) data at baseline across a cohort of: 21 pMCI patients, 33 stable MCI (sMCI) patients, and 29 normal controls. Fast eigenvector centrality mapping (fECM) based on resting-state functional MRI (rsfMRI) was used to investigate brain network organization differences among these groups, and we further assessed its relation to cognition and AD-related pathology...
October 18, 2016: Journal of Alzheimer's Disease: JAD
Yanjia Deng, Kai Liu, Lin Shi, Yi Lei, Peipeng Liang, Kuncheng Li, Winnie C W Chu, Defeng Wang
Patients with mild cognitive impairment (MCI) are at high risk for developing Alzheimer's disease (AD), while some of them may remain stable over decades. The underlying mechanism is still not fully understood. In this study, we aimed to explore the connectivity differences between progressive MCI (PMCI) and stable MCI (SMCI) individuals on a whole-brain scale and on a voxel-wise basis, and we also aimed to reveal the differential dynamic alteration patterns between these two disease subtypes. The resting-state functional magnetic resonance images of PMCI and SMCI patients at baseline and year-one were obtained from the Alzheimer's Disease Neuroimaging Initiative dataset, and the progression was determined based on a 3-year follow-up...
2016: Frontiers in Aging Neuroscience
Luise Christine Löwe, Christian Gaser, Katja Franke
In our aging society, diseases in the elderly come more and more into focus. An important issue in research is Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) with their causes, diagnosis, treatment, and disease prediction. We applied the Brain Age Gap Estimation (BrainAGE) method to examine the impact of the Apolipoprotein E (APOE) genotype on structural brain aging, utilizing longitudinal magnetic resonance image (MRI) data of 405 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database...
2016: PloS One
Joana B Pereira, Mite Mijalkov, Ehsan Kakaei, Patricia Mecocci, Bruno Vellas, Magda Tsolaki, Iwona Kłoszewska, Hilka Soininen, Christian Spenger, Simmon Lovestone, Andrew Simmons, Lars-Olof Wahlund, Giovanni Volpe, Eric Westman
Recent findings suggest that Alzheimer's disease (AD) is a disconnection syndrome characterized by abnormalities in large-scale networks. However, the alterations that occur in network topology during the prodromal stages of AD, particularly in patients with stable mild cognitive impairment (MCI) and those that show a slow or faster progression to dementia, are still poorly understood. In this study, we used graph theory to assess the organization of structural MRI networks in stable MCI (sMCI) subjects, late MCI converters (lMCIc), early MCI converters (eMCIc), and AD patients from 2 large multicenter cohorts: ADNI and AddNeuroMed...
August 2016: Cerebral Cortex
María Eugenia López, Agustín Turrero, Pablo Cuesta, David López-Sanz, Ricardo Bruña, Alberto Marcos, Pedro Gil, Miguel Yus, Ana Barabash, José Antonio Cabranes, Fernando Maestú, Alberto Fernández
Recent proposals of diagnostic criteria within the healthy aging-Alzheimer's disease (AD) continuum stressed the role of biomarker information. More importantly, such information might be critical to predict those mild cognitive impairment (MCI) patients at a higher risk of conversion to AD. Usually, follow-up studies utilize a reduced number of potential markers although the conversion phenomenon may be deemed as multifactorial in essence. In addition, not only biological but also cognitive markers may play an important role...
March 5, 2016: Journal of Alzheimer's Disease: JAD
J Pietschnig, L Schröder, I Ratheiser, I Kryspin-Exner, M Pflüger, D Moser, E Auff, W Pirker, G Pusswald, J Lehrner
BACKGROUND: Impairments in facial emotion recognition (FER) have been detected in patients with Parkinson disease (PD). Presently, we aim at assessing differences in emotion recognition performance in PD patient groups with and without mild forms of cognitive impairment (MCI) compared to healthy controls. METHODS: Performance on a concise emotion recognition test battery (VERT-K) of three groups of 97 PD patients was compared with an age-equivalent sample of 168 healthy controls...
July 2016: International Psychogeriatrics
Lele Xu, Xia Wu, Rui Li, Kewei Chen, Zhiying Long, Jiacai Zhang, Xiaojuan Guo, Li Yao
For patients with mild cognitive impairment (MCI), the likelihood of progression to probable Alzheimer's disease (AD) is important not only for individual patient care, but also for the identification of participants in clinical trial, so as to provide early interventions. Biomarkers based on various neuroimaging modalities could offer complementary information regarding different aspects of disease progression. The current study adopted a weighted multi-modality sparse representation-based classification method to combine data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, from three imaging modalities: Volumetric magnetic resonance imaging (MRI), fluorodeoxyglucose (FDG) positron emission tomography (PET), and florbetapir PET...
2016: Journal of Alzheimer's Disease: JAD
Shorena Janelidze, Joakim Hertze, Henrik Zetterberg, Maria Landqvist Waldö, Alexander Santillo, Kaj Blennow, Oskar Hansson
OBJECTIVE: Widespread implementation of cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) in clinical settings requires improved accuracy for diagnosis of prodromal disease and for distinguishing AD from non-AD dementias. Novel and promising CSF biomarkers include neurogranin, a marker of synaptic degeneration, and YKL-40, a marker of neuroinflammation. METHODS: CSF neurogranin and YKL-40 were measured in a cohort of 338 individuals including cognitively healthy controls and patients with stable mild cognitive impairment (sMCI), MCI who later developed AD (MCI-AD), AD dementia, Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), vascular dementia (VaD), and frontotemporal dementia (FTD)...
January 2016: Annals of Clinical and Translational Neurology
Na Li, Shilpa S Dhar, Tsai-Yu Chen, Pu-Yeh Kan, Yongkun Wei, Jae-Hwan Kim, Chia-Hsin Chan, Hui-Kuan Lin, Mien-Chie Hung, Min Gyu Lee
Entire or partial deletions of the male-specific Y chromosome are associated with tumorigenesis, but whether any male-specific genes located on this chromosome play a tumor-suppressive role is unknown. Here, we report that the histone H3 lysine 4 (H3K4) demethylase JARID1D (also called KDM5D and SMCY), a male-specific protein, represses gene expression programs associated with cell invasiveness and suppresses the invasion of prostate cancer cells in vitro and in vivo. We found that JARID1D specifically repressed the invasion-associated genes MMP1, MMP2, MMP3, MMP7, and Slug by demethylating trimethyl H3K4, a gene-activating mark, at their promoters...
February 15, 2016: Cancer Research
Mingxia Liu, Daoqiang Zhang, Dinggang Shen
As shown in the literature, methods based on multiple templates usually achieve better performance, compared with those using only a single template for processing medical images. However, most existing multi-template based methods simply average or concatenate multiple sets of features extracted from different templates, which potentially ignores important structural information contained in the multi-template data. Accordingly, in this paper, we propose a novel relationship induced multi-template learning method for automatic diagnosis of Alzheimer's disease (AD) and its prodromal stage, i...
June 2016: IEEE Transactions on Medical Imaging
Kim-Han Thung, Chong-Yaw Wee, Pew-Thian Yap, Dinggang Shen
Distinguishing progressive mild cognitive impairment (pMCI) from stable mild cognitive impairment (sMCI) is critical for identification of patients who are at risk for Alzheimer's disease (AD), so that early treatment can be administered. In this paper, we propose a pMCI/sMCI classification framework that harnesses information available in longitudinal magnetic resonance imaging (MRI) data, which could be incomplete, to improve diagnostic accuracy. Volumetric features were first extracted from the baseline MRI scan and subsequent scans acquired after 6, 12, and 18 months...
November 2016: Brain Structure & Function
Istvan Horvath, Xueen Jia, Per Johansson, Chao Wang, Roman Moskalenko, Andreas Steinau, Lars Forsgren, Thomas Wågberg, Johan Svensson, Henrik Zetterberg, Ludmilla A Morozova-Roche
Pro-inflammatory protein S100A9 was established as a biomarker of dementia progression and compared with others such as Aβ(1-42) and tau-proteins. CSF samples from 104 stringently diagnosed individuals divided into five subgroups were analyzed, including nondemented controls, stable mild cognitive impairment (SMCI), mild cognitive impairment due to Alzheimer's disease (MCI-AD), Alzheimer's disease (AD), and vascular dementia (VaD) patients. ELISA, dot-blotting, and electrochemical impedance spectroscopy were used as research methods...
January 20, 2016: ACS Chemical Neuroscience
Per Johansson, Erik G Almqvist, Anders Wallin, Jan-Ove Johansson, Ulf Andreasson, Kaj Blennow, Henrik Zetterberg, Johan Svensson
The neuropeptides substance P, orexin A (hypocretin-1) and neurotensin are signaling molecules that influence brain activity. We examined their cerebrospinal fluid (CSF) levels in a study population consisting of Alzheimer's disease (AD) dementia or mild cognitive impairment (MCI) diagnosed with AD dementia upon follow-up (n=32), stable MCI (SMCI, n=13), other dementias (n=15), and healthy controls (n=20). CSF substance P level was increased in AD patients compared to patients with other dementias and healthy controls (P<0...
November 16, 2015: Neuroscience Letters
Takehiko Doi, Hiroyuki Shimada, Hyuma Makizako, Kota Tsutsumimoto, Ryo Hotta, Sho Nakakubo, Takao Suzuki
OBJECTIVES: Mild cognitive impairment (MCI) may be a risk for disability, and co-occurrence of slow gait (SG) and MCI may increase this risk. DESIGN: Prospective study. SETTING: General community. PARTICIPANTS: The study included 3482 older adults (mean age: 71.4 years) without disability at baseline. MEASUREMENTS: We collected information on demographic variables, measured gait speed and cognitive function to diagnose MCI at baseline...
December 2015: Journal of the American Medical Directors Association
Wong Yu, Ning Jiang, Peter J R Ebert, Brian A Kidd, Sabina Müller, Peder J Lund, Jeremy Juang, Keishi Adachi, Tiffany Tse, Michael E Birnbaum, Evan W Newell, Darrell M Wilson, Gijsbert M Grotenbreg, Salvatore Valitutti, Stephen R Quake, Mark M Davis
It has long been thought that clonal deletion efficiently removes almost all self-specific T cells from the peripheral repertoire. We found that self-peptide MHC-specific CD8(+) T cells in the blood of healthy humans were present in frequencies similar to those specific for non-self antigens. For the Y chromosome-encoded SMCY antigen, self-specific T cells exhibited only a 3-fold lower average frequency in males versus females and were anergic with respect to peptide activation, although this inhibition could be overcome by a stronger stimulus...
May 19, 2015: Immunity
Steven Lawrence Rosinski, Brad Stone, Scott S Graves, Deborah H Fuller, Stephen C De Rosa, Gregory A Spies, Gregory J Mize, James T Fuller, Rainer Storb
BACKGROUND: Minor histocompatibility antigen (miHA) vaccines have the potential to augment graft-versus-tumor effects without graft-versus-host disease (GVHD). We used mixed hematopoietic chimerism in the canine model of major histocompatibility complex-matched allogeneic hematopoietic cell transplantation as a platform to develop a miHA vaccination regimen. METHODS: We engineered DNA plasmids and replication-deficient human adenovirus type 5 constructs encoding large sections of canine SMCY and the entire canine SRY gene...
October 2015: Transplantation
Alberto Redolfi, David Manset, Frederik Barkhof, Lars-Olof Wahlund, Tristan Glatard, Jean-François Mangin, Giovanni B Frisoni
BACKGROUND AND PURPOSE: The measurement of cortical shrinkage is a candidate marker of disease progression in Alzheimer's. This study evaluated the performance of two pipelines: Civet-CLASP (v1.1.9) and Freesurfer (v5.3.0). METHODS: Images from 185 ADNI1 cases (69 elderly controls (CTR), 37 stable MCI (sMCI), 27 progressive MCI (pMCI), and 52 Alzheimer (AD) patients) scanned at baseline, month 12, and month 24 were processed using the two pipelines and two interconnected e-infrastructures: neuGRID (https://neugrid4you...
2015: PloS One
Hideki Nakasone, Lu Tian, Bita Sahaf, Takakazu Kawase, Kelsi Schoenrock, Spenser Perloff, Christine E Ryan, Jed Paul, Rakesh Popli, Fang Wu, Joanne M Otani, John Coller, Edus H Warren, David B Miklos
Allogeneic antibodies against minor histocompatibility antigens encoded on the Y chromosome (HY-Abs) develop after hematopoietic cell transplant (HCT) of male recipients with female donors (F→M). However, the temporal association between HY-Ab development and chronic graft-versus-host disease (cGVHD) has yet to be elucidated. We studied 136 adult F→M HCT patients, with plasma prospectively collected through 3 years posttransplant, and measured immunoglobulin G against 6 H-Y antigens. Multiple HY-Abs were frequently detected beginning at 3 months posttransplant: 78 (57%) of F→M patients were seropositive for at least 1 of the 6 HY-Abs, and 3-month seropositivity for each HY-Ab was associated with a persistent seropositive response throughout the posttransplant follow-up period (P < ...
May 14, 2015: Blood
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