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https://www.readbyqxmd.com/read/28105773/exosomal-biomarkers-of-brain-insulin-resistance-associated-with-regional-atrophy-in-alzheimer-s-disease
#1
Roger J Mullins, Maja Mustapic, Edward J Goetzl, Dimitrios Kapogiannis
: Brain insulin resistance (IR), which depends on insulin-receptor-substrate-1 (IRS-1) phosphorylation, is characteristic of Alzheimer's disease (AD). Previously, we demonstrated higher pSer312-IRS-1 (ineffective insulin signaling) and lower p-panTyr-IRS-1 (effective insulin signaling) in neural origin-enriched plasma exosomes of AD patients vs. CONTROLS: Here, we hypothesized that these exosomal biomarkers associate with brain atrophy in AD. We studied 24 subjects with biomarker-supported probable AD (low CSF Aβ42 )...
January 20, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28103595/identification-of-small-peptides-in-human-cerebrospinal-fluid-upon-amyloid-%C3%AE-degradation
#2
Naoki Mizuta, Kanta Yanagida, Takashi Kodama, Takeshi Tomonaga, Mako Takami, Hiroshi Oyama, Takashi Kudo, Manabu Ikeda, Masatoshi Takeda, Shinji Tagami, Masayasu Okochi
BACKGROUND: Amyloid-β (Aβ) degradation in brains of Alzheimer disease patients is a crucial focus for the clarification of disease pathogenesis. Nevertheless, the mechanisms underlying Aβ degradation in the human brain remain unclear. OBJECTIVE: This study aimed to quantify the levels of small C-terminal Aβ fragments generated upon Aβ degradation in human cerebrospinal fluid (CSF). METHODS: A fraction containing small peptides was isolated and purified from human CSF by high-pressure liquid chromatography...
January 20, 2017: Neuro-degenerative Diseases
https://www.readbyqxmd.com/read/28089353/cerebrospinal-fluid-mitochondrial-dna-in-the-alzheimer-s-disease-continuum
#3
Laura Cervera-Carles, Daniel Alcolea, Ainara Estanga, Mirian Ecay-Torres, Andrea Izagirre, Montserrat Clerigué, Maite García-Sebastián, Jorge Villanúa, Clàudia Escalas, Rafael Blesa, Pablo Martínez-Lage, Alberto Lleó, Juan Fortea, Jordi Clarimón
Low levels of cell-free mitochondrial DNA (mtDNA) in the cerebrospinal fluid (CSF) of Alzheimer's disease (AD) patients have been identified and proposed as a novel biomarker for the disease. The lack of validation studies of previous results prompted us to replicate this finding in a comprehensive series of patients and controls. We applied droplet digital polymerase chain reaction in CSF specimens from 124 patients representing the AD spectrum and 140 neurologically healthy controls. The following preanalytical and analytical parameters were evaluated: the effect of freeze-thaw cycles on mtDNA, the linearity of mtDNA load across serial dilutions, and the mtDNA levels in the diagnostic groups...
December 22, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28086917/resveratrol-regulates-neuro-inflammation-and-induces-adaptive-immunity-in-alzheimer-s-disease
#4
Charbel Moussa, Michaeline Hebron, Xu Huang, Jaeil Ahn, Robert A Rissman, Paul S Aisen, R Scott Turner
BACKGROUND: Treatment of mild-moderate Alzheimer's disease (AD) subjects (N = 119) for 52 weeks with the SIRT1 activator resveratrol (up to 1 g by mouth twice daily) attenuates progressive declines in CSF Aβ40 levels and activities of daily living (ADL) scores. METHODS: For this retrospective study, we examined banked CSF and plasma samples from a subset of AD subjects with CSF Aβ42 <600 ng/ml (biomarker-confirmed AD) at baseline (N = 19 resveratrol-treated and N = 19 placebo-treated)...
January 3, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28072416/preclinical-amyloid-pathology-biomarker-positivity-effects-on-tau-pathology-and-neurodegeneration
#5
K Höglund, S Kern, A Zettergren, A Börjesson-Hansson, H Zetterberg, I Skoog, K Blennow
Brain autopsy and biomarker studies indicate that the pathology of Alzheimer's disease (AD) is initiated at least 10-20 years before clinical symptoms. This provides a window of opportunity to initiate preventive treatment. However, this emphasizes the necessity for biomarkers that identify individuals at risk for developing AD later in life. In this cross-sectional study, originating from three epidemiologic studies in Sweden (n=1428), the objective was to examine whether amyloid pathology, as determined by low cerebrospinal fluid (CSF) concentration of the 42 amino acid form of β-amyloid (Aβ42), is associated with biomarker evidence of other pathological changes in cognitively healthy elderly...
January 10, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28071698/increased-levels-of-csf-total-but-not-oligomeric-or-phosphorylated-forms-of-alpha-synuclein-in-patients-diagnosed-with-probable-alzheimer-s-disease
#6
Nour K Majbour, Davide Chiasserini, Nishant N Vaikath, Paolo Eusebi, Takahiko Tokuda, Wilma van de Berg, Lucilla Parnetti, Paolo Calabresi, Omar M A El-Agnaf
Several studies reported an association between CSF alpha-synuclein (α-syn) and tau in Alzheimer's disease (AD), and demonstrated the significance of α-syn in improving the diagnostic sensitivity/specificity of classical AD CSF biomarkers. In the current study, we measured CSF levels of different α-syn species in a cohort of AD patients (n = 225) who showed a CSF profile typical of AD at baseline as well as in cognitively intact controls (n = 68). CSF total α-syn (t-α-syn) significantly increased in the AD group (p < 0...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28070672/opposing-effects-of-progranulin-deficiency-on-amyloid-and-tau-pathologies-via-microglial-tyrobp-network
#7
Hideyuki Takahashi, Zoe A Klein, Sarah M Bhagat, Adam C Kaufman, Mikhail A Kostylev, Tsuneya Ikezu, Stephen M Strittmatter
Progranulin (PGRN) is implicated in Alzheimer's disease (AD) as well as frontotemporal lobar degeneration. Genetic studies demonstrate an association of the common GRN rs5848 variant that results in reduced PGRN levels with increased risk for AD. However, the mechanisms by which PGRN reduction from the GRN AD risk variant or mutation exacerbates AD pathophysiology remain ill defined. Here, we show that the GRN AD risk variant has no significant effects on florbetapir positron emission tomographic amyloid imaging and cerebrospinal fluid (CSF) Aβ levels, whereas it is associated with increased CSF tau levels in human subjects of the Alzheimer's disease neuroimaging initiative studies...
January 9, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28069930/a-quantitative-analysis-of-brain-soluble-tau-and-the-tau-secretion-factor
#8
Pengcheng Han, Geidy Serrano, Thomas G Beach, Richard J Caselli, Junxiang Yin, Ningning Zhuang, Jiong Shi
Neurofibrillary tangles (NFTs) represent products of insoluble tau protein in the brains of patients with Alzheimer disease (AD). The cerebrospinal fluid (CSF) tau level is a biomarker in AD diagnosis. The soluble portion of tau protein in brain parenchyma is presumably the source for CSF tau but this has not previously been quantified. We measured CSF tau and soluble brain tau at autopsy in temporal and frontal brain tissue samples from 7 cognitive normal, 12 mild cognitively impaired, and 19 AD subjects. Based on the measured brain soluble tau, we calculated the whole brain tau load and estimated tau secretion factor...
January 9, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28067307/fluorescent-gold-nanoclusters-for-selective-detection-of-dopamine-in-cerebrospinal-fluid
#9
Saravanan Govindaraju, Seshadri Reddy Ankireddy, Buddolla Viswanath, Jongsung Kim, Kyusik Yun
Since the last two decades, protein conjugated fluorescent gold nanoclusters (NCs) owe much attention in the field of medical and nanobiotechnology due to their excellent photo stability characteristics. In this paper, we reported stable, nontoxic and red fluorescent emission BSA-Au NCs for selective detection of L-dopamine (DA) in cerebrospinal fluid (CSF). The evolution was probed by various instrumental techniques such as UV-vis spectroscopy, High resolution transmission electron microscopy (HTEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), photoluminescence spectroscopy (PL)...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28066842/diagnosis-of-alzheimer-s-disease-using-view-aligned-hypergraph-learning-with-incomplete-multi-modality-data
#10
Mingxia Liu, Jun Zhang, Pew-Thian Yap, Dinggang Shen
Effectively utilizing incomplete multi-modality data for diagnosis of Alzheimer's disease (AD) is still an area of active research. Several multi-view learning methods have recently been developed to deal with missing data, with each view corresponding to a specific modality or a combination of several modalities. However, existing methods usually ignore the underlying coherence among views, which may lead to suboptimal learning performance. In this paper, we propose a view-aligned hypergraph learning (VAHL) method to explicitly model the coherence among the views...
October 2016: Medical Image Computing and Computer-assisted Intervention: MICCAI ..
https://www.readbyqxmd.com/read/28062720/multimodal-characterization-of-older-apoe2-carriers-reveals-selective-reduction-of-amyloid-load
#11
Michel J Grothe, Sylvia Villeneuve, Martin Dyrba, David Bartrés-Faz, Miranka Wirth
OBJECTIVE: To comprehensively assess neurobiological effects of the protective APOE2 allele in the aged brain using a cross-sectional multimodal neuroimaging approach. METHODS: Multimodal neuroimaging data were obtained from a total of 572 older individuals without dementia (cognitively normal and mild cognitive impairment) enrolled in the Alzheimer's Disease Neuroimaging Initiative and included assessments of regional amyloid load with AV45-PET, glucose metabolism with fluorodeoxyglucose-PET, and gray matter volume with structural MRI...
January 6, 2017: Neurology
https://www.readbyqxmd.com/read/28061383/increased-blood-brain-barrier-permeability-is-associated-with-dementia-and-diabetes-but-not-amyloid-pathology-or-apoe-genotype
#12
Shorena Janelidze, Joakim Hertze, Katarina Nägga, Karin Nilsson, Christer Nilsson, Malin Wennström, Danielle van Westen, Kaj Blennow, Henrik Zetterberg, Oskar Hansson
Blood-brain barrier (BBB) dysfunction might be an important component of many neurodegenerative disorders. In this study, we investigated its role in dementia using large clinical cohorts. The cerebrospinal fluid (CSF)/plasma albumin ratio (Qalb), an indicator of BBB (and blood-CSF barrier) permeability, was measured in a total of 1015 individuals. The ratio was increased in patients with Alzheimer's disease, dementia with Lewy bodies or Parkinson's disease dementia, subcortical vascular dementia, and frontotemporal dementia compared with controls...
December 5, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28059783/improved-cerebrospinal-fluid-based-discrimination-between-alzheimer-s-disease-patients-and-controls-after-correction-for-ventricular-volumes
#13
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/28054724/learning-based-3t-brain-mri-segmentation-with-guidance-from-7t-mri-labeling
#14
Minghui Deng, Renping Yu, Li Wang, Feng Shi, Pew-Thian Yap, Dinggang Shen
PURPOSE: Segmentation of brain magnetic resonance (MR) images into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) is crucial for brain structural measurement and disease diagnosis. Learning-based segmentation methods depend largely on the availability of good training ground truth. However, the commonly used 3T MR images are of insufficient image quality and often exhibit poor intensity contrast between WM, GM, and CSF. Therefore, they are not ideal for providing good ground truth label data for training learning-based methods...
December 2016: Medical Physics
https://www.readbyqxmd.com/read/28054371/review-tau-in-biofluids-relation-to-pathology-imaging-and-clinical-features
#15
Henrik Zetterberg
Tau is a microtubule-binding protein that is important for the stability of neuronal axons. It is normally expressed within neurons and is also secreted into the brain interstitial fluid that communicates freely with cerebrospinal fluid (CSF) and, in a more restricted manner, blood via the glymphatic clearance system of the brain. In Alzheimer's disease (AD), neuroaxonal degeneration results in increased release of tau from neurons. Further, tau is truncated and phosphorylated, which leads to aggregation of tau in neurofibrillary tangles of the proximal axoplasm...
January 5, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/28042517/rust-on-the-brain-from-microbleeds-and-its-relevance-to-alzheimer-studies-invited-commentary-on-cacciottolo-neurobiology-of-aging-2016
#16
M Cacciottolo, T E Morgan, C E Finch
Cerebral microbleeds (MB) and small vessel disease (SVD) with congophilic arterial angiopathy (CAA) are increasingly recognized as a variable factor in AD cognitive impairments. This commentary on our recent report on sex-ApoE interactions in MBs published this February, briefly explores three aspects of MBs that could not be fully discussed therein: I, A possible gap between the prevalence of MBs as detected by MRI and post mortem analysis; II, The role of hemoglobin-degradation products in amyloid-attributed neurodegenerative changes; and III, Possible assessment of MB by cerebrospinal fluid (CSF) assays for iron-related markers to better screen patient subgroups for AD interventions...
November 2016: Journal of Alzheimer's Disease and Parkinsonism
https://www.readbyqxmd.com/read/28035921/young-to-middle-aged-dogs-with-high-amyloid-%C3%AE-levels-in-cerebrospinal-fluid-are-impaired-on-learning-in-standard-cognition-tests
#17
Herman Borghys, Bianca Van Broeck, Deborah Dhuyvetter, Tom Jacobs, Katja de Waepenaert, Tim Erkens, Melissa Brooks, Sandy Thevarkunnel, Joseph A Araujo
Understanding differences in Alzheimer's disease biomarkers before the pathology becomes evident can contribute to an improved understanding of disease pathogenesis and treatment. A decrease in amyloid-β (Aβ)42 in cerebrospinal fluid (CSF) is suggested to be a biomarker for Aβ deposition in brain. However, the relevance of CSF Aβ levels prior to deposition is not entirely known. Dogs are similar to man with respect to amyloid-β protein precursor (AβPP)-processing, age-related amyloid plaque deposition, and cognitive dysfunction...
December 30, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28035918/apolipoprotein-a1-in-cerebrospinal-fluid-and-plasma-and-progression-to-alzheimer-s-disease-in-non-demented-elderly
#18
Rosalinde E R Slot, Argonde C Van Harten, Maartje I Kester, Wesley Jongbloed, Femke H Bouwman, Charlotte E Teunissen, Philip Scheltens, Robert Veerhuis, Wiesje M van der Flier
BACKGROUND: HDL-cholesterol transporter Apolipoprotein A1 (ApoA1) holds neuroprotective properties, such as inhibition of amyloid-β aggregation. Low plasma ApoA1 concentrations are associated with Alzheimer's disease (AD). Little is known about ApoA1 levels in the pre-dementia stages of AD. OBJECTIVE: To investigate associations between cerebrospinal fluid (CSF) and plasma ApoA1 levels and clinical progression toward AD in non-demented elderly. METHODS: From the Amsterdam Dementia Cohort, we included 429 non-demented elderly with subjective cognitive decline (SCD; n = 206, 61±9 years, Mini-Mental State Exam (MMSE) 28±2) and mild cognitive impairment (MCI; n = 223, 67±8 years, MMSE 27±2), with a mean follow-up of 2...
December 30, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28035842/clinical-and-cost-implications-of-beta-amyloid-detection-with-a%C3%AE-pet-imaging-in-early-alzheimer-s-disease-the-case-of-florbetapir
#19
John Hornberger, Jay Bae, Ian Watson, Joe Johnston, Michael Happich
OBJECTIVE: Amyloid-β (Aβ) positron emission tomography (PET) imaging helps estimate Aβ neuritic plaque density in patients with cognitive impairment who are under evaluation for Alzheimer's disease (AD). This study aims to evaluate the cost-effectiveness of the Aβ-PET scan as an adjunct to standard diagnostic assessment for diagnosis of AD in France, using florbetapir as an example. METHODS: A state-transition probability analysis was developed adopting the French Health Technology Assessment (HTA) perspective per guidance...
December 30, 2016: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28033566/towards-a-holistic-cortical-thickness-descriptor-heat-kernel-based-grey-matter-morphology-signatures
#20
Gang Wang, Yalin Wang
In this paper, we propose a heat kernel based regional shape descriptor that may be capable of better exploiting volumetric morphological information than other available methods, thereby improving statistical power on brain magnetic resonance imaging (MRI) analysis. The mechanism of our analysis is driven by the graph spectrum and the heat kernel theory, to capture the volumetric geometry information in the constructed tetrahedral meshes. In order to capture profound brain grey matter shape changes, we first use the volumetric Laplace-Beltrami operator to determine the point pair correspondence between white-grey matter and CSF-grey matter boundary surfaces by computing the streamlines in a tetrahedral mesh...
December 26, 2016: NeuroImage
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