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Alzheimer biomarker

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https://www.readbyqxmd.com/read/28346578/association-of-plasma-neurofilament-light-with-neurodegeneration-in-patients-with-alzheimer-disease
#1
Niklas Mattsson, Ulf Andreasson, Henrik Zetterberg, Kaj Blennow
Importance: Existing cerebrospinal fluid (CSF) or imaging (tau positron emission tomography) biomarkers for Alzheimer disease (AD) are invasive or expensive. Biomarkers based on standard blood test results would be useful in research, drug development, and clinical practice. Plasma neurofilament light (NFL) has recently been proposed as a blood-based biomarker for neurodegeneration in dementias. Objective: To test whether plasma NFL concentrations are increased in AD and associated with cognitive decline, other AD biomarkers, and imaging evidence of neurodegeneration...
March 27, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28345017/proof-of-concept-demonstration-of-optimal-composite-mri-endpoints-for-clinical-trials
#2
Steven D Edland, M Colin Ard, Jaiashre Sridhar, Derin Cobia, Adam Martersteck, M Marsel Mesulam, Emily J Rogalski
BACKGROUND: Atrophy measures derived from structural MRI are promising outcome measures for early phase clinical trials, especially for rare diseases such as primary progressive aphasia (PPA), where the small available subject pool limits our ability to perform meaningfully powered trials with traditional cognitive and functional outcome measures. METHODS: We investigated a composite atrophy index in 26 PPA participants with longitudinal MRIs separated by two years...
September 2016: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/28344933/precision-medicine-the-golden-gate-for-detection-treatment-and-prevention-of-alzheimer-s-disease
#3
H Hampel, S E O'Bryant, J I Castrillo, C Ritchie, K Rojkova, K Broich, N Benda, R Nisticò, R A Frank, B Dubois, V Escott-Price, S Lista
During this decade, breakthrough conceptual shifts have commenced to emerge in the field of Alzheimer's disease (AD) recognizing risk factors and the non-linear dynamic continuum of complex pathophysiologies amongst a wide dimensional spectrum of multi-factorial brain proteinopathies/neurodegenerative diseases. As is the case in most fields of medicine, substantial advancements in detecting, treating and preventing AD will likely evolve from the generation and implementation of a systematic precision medicine strategy...
December 2016: Journal of Prevention of Alzheimer's Disease
https://www.readbyqxmd.com/read/28344552/adding-recognition-discriminability-index-to-the-delayed-recall-is-useful-to-predict-conversion-from-mild-cognitive-impairment-to-alzheimer-s-disease-in-the-alzheimer-s-disease-neuroimaging-initiative
#4
María J Russo, Jorge Campos, Silvia Vázquez, Gustavo Sevlever, Ricardo F Allegri
Background: Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to Alzheimer's disease (AD). We investigated whether recognition memory tasks in combination with delayed recall measure of episodic memory and CSF biomarkers can predict MCI to AD conversion at 24-month follow-up. Methods: A total of 397 amnestic-MCI subjects from Alzheimer's disease Neuroimaging Initiative were included. Logistic regression modeling was done to assess the predictive value of all RAVLT measures, risk factors such as age, sex, education, APOE genotype, and CSF biomarkers for progression to AD...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28342882/functional-neuroimaging-findings-in-healthy-middle-aged-adults-at-risk-of-alzheimer-s-disease
#5
REVIEW
Mirette Habib, Elijah Mak, Silvy Gabel, Li Su, Guy Williams, Adam Waldman, Katie Wells, Karen Ritchie, Craig Ritchie, John T O'Brien
It is well established that the neurodegenerative process of Alzheimer's disease (AD) begins many years before symptom onset. This preclinical phase provides a crucial time-window for therapeutic intervention, though this requires biomarkers that could evaluate the efficacy of future disease-modification treatments in asymptomatic individuals. The last decade has witnessed a proliferation of studies characterizing the temporal sequence of the earliest functional and structural brain imaging changes in AD. These efforts have focused on studying individuals who are highly vulnerable to develop AD, such as those with familial genetic mutations, susceptibility genes (i...
March 22, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28342697/recent-publications-from-the-alzheimer-s-disease-neuroimaging-initiative-reviewing-progress-toward-improved-ad-clinical-trials
#6
REVIEW
Michael W Weiner, Dallas P Veitch, Paul S Aisen, Laurel A Beckett, Nigel J Cairns, Robert C Green, Danielle Harvey, Clifford R Jack, William Jagust, John C Morris, Ronald C Petersen, Andrew J Saykin, Leslie M Shaw, Arthur W Toga, John Q Trojanowski
INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative (ADNI) has continued development and standardization of methodologies for biomarkers and has provided an increased depth and breadth of data available to qualified researchers. This review summarizes the 450+ publications using ADNI data during 2014 and 2015. METHODS: We used standard searches to find publications using ADNI data. RESULTS: (1) Structural and functional changes, including subtle changes to hippocampal shape and texture, atrophy in areas outside of hippocampus, and disruption to functional networks, are detectable in presymptomatic subjects before hippocampal atrophy; (2) In subjects with abnormal β-amyloid deposition (Aβ+), biomarkers become abnormal in the order predicted by the amyloid cascade hypothesis; (3) Cognitive decline is more closely linked to tau than Aβ deposition; (4) Cerebrovascular risk factors may interact with Aβ to increase white-matter (WM) abnormalities which may accelerate Alzheimer's disease (AD) progression in conjunction with tau abnormalities; (5) Different patterns of atrophy are associated with impairment of memory and executive function and may underlie psychiatric symptoms; (6) Structural, functional, and metabolic network connectivities are disrupted as AD progresses...
March 22, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28341999/immunological-memory-to-hyperphosphorylated-tau-in-asymptomatic-individuals
#7
Gabriel Pascual, Jehangir S Wadia, Xueyong Zhu, Elissa Keogh, Başak Kükrer, Jeroen van Ameijde, Hanna Inganäs, Berdien Siregar, Gerrard Perdok, Otto Diefenbach, Tariq Nahar, Imke Sprengers, Martin H Koldijk, Els C Brinkman-van der Linden, Laura A Peferoen, Heng Zhang, Wenli Yu, Xinyi Li, Michelle Wagner, Veronica Moreno, Julie Kim, Martha Costa, Kiana West, Zara Fulton, Lucy Chammas, Nancy Luckashenak, Lauren Fletcher, Trevin Holland, Carrie Arnold, R Anthony Williamson, Jeroen J Hoozemans, Adrian Apetri, Frederique Bard, Ian A Wilson, Wouter Koudstaal, Jaap Goudsmit
Several reports have described the presence of antibodies against Alzheimer's disease-associated hyperphosphorylated forms of tau in serum of healthy individuals. To characterize the specificities that can be found, we interrogated peripheral IgG(+) memory B cells from asymptomatic blood donors for reactivity to a panel of phosphorylated tau peptides using a single-cell screening assay. Antibody sequences were recovered, cloned, and expressed as full-length IgGs. In total, 52 somatically mutated tau-binding antibodies were identified, corresponding to 35 unique clonal families...
March 24, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28341718/relationships-among-cortical-glutathione-levels-brain-amyloidosis-and-memory-in-healthy-older-adults-investigated-in-vivo-with-1-h-mrs-and-pittsburgh-compound-b-pet
#8
G C Chiang, X Mao, G Kang, E Chang, S Pandya, S Vallabhajosula, R Isaacson, L D Ravdin, D C Shungu
BACKGROUND AND PURPOSE: Oxidative stress has been implicated as an important pathologic mechanism in the development of Alzheimer disease. The purpose of this study was to assess whether glutathione levels, detected noninvasively with proton MR spectroscopy, are associated with brain amyloidosis and memory in a community-dwelling cohort of healthy older adults. MATERIALS AND METHODS: Fifteen cognitively healthy subjects were prospectively enrolled in this study...
March 24, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28341646/cardiorespiratory-fitness-alters-the-influence-of-a-polygenic-risk-score-on-biomarkers-of-ad
#9
Stephanie A Schultz, Elizabeth A Boots, Burcu F Darst, Henrik Zetterberg, Kaj Blennow, Dorothy F Edwards, Rebecca L Koscik, Cynthia M Carlsson, Catherine L Gallagher, Barbara B Bendlin, Sanjay Asthana, Mark A Sager, Kirk J Hogan, Bruce P Hermann, Dane B Cook, Sterling C Johnson, Corinne D Engelman, Ozioma C Okonkwo
OBJECTIVE: To examine whether a polygenic risk score (PRS) derived from APOE4, CLU, and ABCA7 is associated with CSF biomarkers of Alzheimer disease (AD) pathology and whether higher cardiorespiratory fitness (CRF) modifies the association between the PRS and CSF biomarkers. METHODS: Ninety-five individuals from the Wisconsin Registry for Alzheimer's Prevention were included in these cross-sectional analyses. They were genotyped for APOE4, CLU, and ABCA7, from which a PRS was calculated for each participant...
March 24, 2017: Neurology
https://www.readbyqxmd.com/read/28341160/metabolic-network-failures-in-alzheimer-s-disease-a-biochemical-road%C3%A2-map
#10
Jon B Toledo, Matthias Arnold, Gabi Kastenmüller, Rui Chang, Rebecca A Baillie, Xianlin Han, Madhav Thambisetty, Jessica D Tenenbaum, Karsten Suhre, J Will Thompson, Lisa St John-Williams, Siamak MahmoudianDehkordi, Daniel M Rotroff, John R Jack, Alison Motsinger-Reif, Shannon L Risacher, Colette Blach, Joseph E Lucas, Tyler Massaro, Gregory Louie, Hongjie Zhu, Guido Dallmann, Kristaps Klavins, Therese Koal, Sungeun Kim, Kwangsik Nho, Li Shen, Ramon Casanova, Sudhir Varma, Cristina Legido-Quigley, M Arthur Moseley, Kuixi Zhu, Marc Y R Henrion, Sven J van der Lee, Amy C Harms, Ayse Demirkan, Thomas Hankemeier, Cornelia M van Duijn, John Q Trojanowski, Leslie M Shaw, Andrew J Saykin, Michael W Weiner, P Murali Doraiswamy, Rima Kaddurah-Daouk
INTRODUCTION: The Alzheimer's Disease Research Summits of 2012 and 2015 incorporated experts from academia, industry, and nonprofit organizations to develop new research directions to transform our understanding of Alzheimer's disease (AD) and propel the development of critically needed therapies. In response to their recommendations, big data at multiple levels are being generated and integrated to study network failures in disease. We used metabolomics as a global biochemical approach to identify peripheral metabolic changes in AD patients and correlate them to cerebrospinal fluid pathology markers, imaging features, and cognitive performance...
March 21, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28341066/recommendations-for-cerebrospinal-fluid-alzheimer-s-disease-biomarkers-in-the-diagnostic-evaluation-of-mild-cognitive-impairment
#11
Sanna-Kaisa Herukka, Anja Hviid Simonsen, Niels Andreasen, Ines Baldeiras, Maria Bjerke, Kaj Blennow, Sebastiaan Engelborghs, Giovanni B Frisoni, Tomasz Gabryelewicz, Samantha Galluzzi, Ron Handels, Milica G Kramberger, Agnieszka Kulczyńska, Jose Luis Molinuevo, Barbara Mroczko, Agneta Nordberg, Catarina Resende Oliveira, Markus Otto, Juha O Rinne, Uroš Rot, Esen Saka, Hilkka Soininen, Hanne Struyfs, Silvia Suardi, Pieter Jelle Visser, Bengt Winblad, Henrik Zetterberg, Gunhild Waldemar
This article presents recommendations, based on the Grading of Recommendations, Assessment, Development, and Evaluation method, for the clinical application of cerebrospinal fluid (CSF) amyloid-β1-42, tau, and phosphorylated tau in the diagnostic evaluation of patients with mild cognitive impairment (MCI). The recommendations were developed by a multidisciplinary working group and based on the available evidence and consensus from focused group discussions for 1) prediction of clinical progression to Alzheimer's disease (AD) dementia, 2) cost-effectiveness, 3) interpretation of results, and 4) patient counseling...
March 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28341065/recommendations-for-csf-ad-biomarkers-in-the-diagnostic-evaluation%C3%A2-of-dementia
#12
Anja Hviid Simonsen, Sanna-Kaisa Herukka, Niels Andreasen, Ines Baldeiras, Maria Bjerke, Kaj Blennow, Sebastiaan Engelborghs, Giovanni B Frisoni, Tomasz Gabryelewicz, Samantha Galluzzi, Ron Handels, Milica G Kramberger, Agnieszka Kulczyńska, Jose Luis Molinuevo, Barbara Mroczko, Agneta Nordberg, Catarina Resende Oliveira, Markus Otto, Juha O Rinne, Uroš Rot, Esen Saka, Hilkka Soininen, Hanne Struyfs, Silvia Suardi, Pieter Jelle Visser, Bengt Winblad, Henrik Zetterberg, Gunhild Waldemar
This article presents recommendations, based on the Grading of Recommendations, Assessment, Development, and Evaluation method, for the clinical application of cerebrospinal fluid (CSF) amyloid-β1-42, tau, and phosphorylated tau in the diagnostic evaluation of patients with dementia. The recommendations were developed by a multidisciplinary working group based on the available evidence and consensus from focused discussions for (i) identification of Alzheimer's disease (AD) as the cause of dementia, (ii) prediction of rate of decline, (iii) cost-effectiveness, and (iv) interpretation of results...
March 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28338847/paradigm-shift-from-diagnosing-patients-based-on-common-symptoms-to-categorizing-patients-into-subtypes-with-different-pathogenic-mechanisms-to-guide-treatment-for-alzheimer-s-disease
#13
Keiro Shirotani, Masashi Asai, Nobuhisa Iwata
Alzheimer's disease (AD) is a major cause of dementia in the elderly, and the number of AD patients is rapidly growing as life expectancy increases. However, disease-modifying drugs are not yet available. According to the amyloid hypothesis, disease onset is triggered by aggregation and accumulation of amyloid-β peptide, followed by formation of neurofibrillary tangles composed of hyperphosphorylated tau, and synaptic loss/neuronal cell death leading to dementia. Based on this hypothesis, various clinical trials for treatment of AD have been conducted, but most were discontinued due to failure to achieve cognitive improvement or appearance of adverse effects...
March 7, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28336779/validation-of-the-semi-quantitative-static-suvr-method-for-18-f-av45-pet-by-pharmacokinetic-modeling-with-an-arterial-input-function
#14
Julie Ottoy, Jeroen Verhaeghe, Ellis Niemantsverdriet, Leonie Wyffels, Charisse Somers, Ellen De Roeck, Hanne Struyfs, Femke Soetewey, Steven Deleye, Tobi Van den Bossche, Sara Van Mossevelde, Sarah Ceyssens, Jan Versijpt, Sigrid Stroobants, Sebastiaan Engelborghs, Steven Staelens
Increased brain uptake of [(18)F]-AV45 visualized by PET is a key biomarker for Alzheimer's disease (AD). The standardized uptake value ratio (SUVR) is widely used for quantification, but is subject to variability based on choice of reference region and changes in cerebral blood flow. Here we validate the SUVR method against the gold standard volume of distribution (VT) to assess cross-sectional differences in plaque load. Methods: Dynamic 60-min [(18)F]-AV45 (291 ± 67 MBq) and 1-min [(15)O]-H2O (370 MBq) scans were obtained in 35 age-matched elderly subjects, including 10 probable AD dementia, 15 amnestic mild cognitive impairment (aMCI) and 10 cognitively healthy controls (HC)...
March 23, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28336337/mismatch-negativity-as-a-potential-neurobiological-marker-of-early-stage-alzheimer-disease-and-vascular-dementia
#15
Shixiang Jiang, Chang Yan, Zhengxue Qiao, Haiqian Yao, Shiquan Jiang, Xiaohui Qiu, Xiuxian Yang, Deyu Fang, Yanjie Yang, Limei Zhang, Lina Wang, Liming Zhang
Alzheimer's disease (AD) and vascular dementia (VD) are serious, irreversible forms of cognitive impairment, which means that an early diagnosis is essential to slow down their progression. One potential neurophysiological biomarker of these diseases is the mismatch negativity (MMN) event-related potentials (ERP) component, which reflects an automatic detection mechanism at the pre-attentive stages of information processing. We evaluated the auditory MMN response in individuals from two patient groups: those in the prodromal stages of AD (P-AD) and those in the prodromal stages of VD (P-VD)...
March 20, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28334990/insulin-resistance-and-exendin-4-treatment-for-multiple-system-atrophy
#16
Fares Bassil, Marie-Hélène Canron, Anne Vital, Erwan Bezard, Yazhou Li, Nigel H Greig, Seema Gulyani, Dimitrios Kapogiannis, Pierre-Olivier Fernagut, Wassilios G Meissner
Multiple system atrophy is a fatal sporadic adult-onset neurodegenerative disorder with no symptomatic or disease-modifying treatment available. The cytopathological hallmark of multiple system atrophy is the accumulation of α-synuclein aggregates in oligodendrocytes, forming glial cytoplasmic inclusions. Impaired insulin/insulin-like growth factor-1 signalling (IGF-1) and insulin resistance (i.e. decreased insulin/IGF-1) have been reported in other neurodegenerative disorders such as Alzheimer's disease. Increasing evidence also suggests impaired insulin/IGF-1 signalling in multiple system atrophy, as corroborated by increased insulin and IGF-1 plasma concentrations in multiple system atrophy patients and reduced IGF-1 brain levels in a transgenic mouse model of multiple system atrophy...
March 14, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28333036/apoe-%C3%AE%C2%B54-specific-imbalance-of-arachidonic-acid-and-docosahexaenoic-acid-in-serum-phospholipids-identifies-individuals-with-preclinical-mild-cognitive-impairment-alzheimer-s-disease
#17
Laila Abdullah, James E Evans, Tanja Emmerich, Gogce Crynen, Ben Shackleton, Andrew P Keegan, Cheryl Luis, Leon Tai, Mary J LaDu, Michael Mullan, Fiona Crawford, Corbin Bachmeier
This study was designed to explore the influence of apolipoprotein E (APOE) on blood phospholipids (PL) in predicting preclinical Alzheimer's disease (AD). Lipidomic analyses were also performed on blood from an AD mouse model expressing human APOE isoforms (EFAD) and five AD mutations and from 195 cognitively normal participants, 23 of who converted to mild cognitive impairment (MCI)/AD within 3 years. APOE ε4-carriers converting to MCI/AD had high arachidonic acid (AA)/docosahexaenoic acid (DHA) ratios in PL compared to cognitively normal ε4 and non-ε4 carriers...
March 23, 2017: Aging
https://www.readbyqxmd.com/read/28330539/-state-of-the-art-work-up-of-dementia-disorder
#18
Steen Gregers Hasselbalch
Early diagnosis of a dementia disorder is required for early support, treatment and information. A basic programme including history taking, somatic and neurological examination, blood screening and a structural scan will suffice in typical cases. For patients with uncertain or atypical symptoms or disease course, supplementary investigations are warranted, including biomarkers in cerebrospinal fluid, functional imaging and neuropsychological testing. Also, imaging of specific protein accumulations in Alzheimer's disease may serve to monitor disease progression and effects of interventions...
March 20, 2017: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/28330509/chemically-treated-plasma-a%C3%AE-is-a-potential-blood-based-biomarker-for-screening-cerebral-amyloid-deposition
#19
Jong-Chan Park, Sun-Ho Han, Hyun Jin Cho, Min Soo Byun, Dahyun Yi, Young Min Choe, Seokjo Kang, Eun Sun Jung, Su Jin Won, Eun Hye Kim, Yu Kyeong Kim, Dong Young Lee, Inhee Mook-Jung
BACKGROUND: Plasma β-amyloid (Aβ) is a potential candidate for an Alzheimer's disease (AD) biomarker because blood is an easily accessible bio-fluid, which can be collected routinely, and Aβ is one of the major hallmarks of AD pathogenesis in the brain. However, the association between plasma Aβ levels and AD diagnosis is still unclear due to the instability and inaccurate measurements of plasma Aβ levels in the blood of patients with AD. If a consistent value of plasma Aβ from the blood can be obtained, this might help determine whether plasma Aβ is a potential biomarker for AD diagnosis...
March 22, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28329084/obstructive-sleep-apnea-is-associated-with-early-but-possibly-modifiable-alzheimer-s-disease-changes
#20
Claudio Liguori, Nicola Biagio Mercuri, Francesca Izzi, Andrea Romigi, Alberto Cordella, Giuseppe Sancesario, Fabio Placidi
Study Objectives: Obstructive sleep apnea (OSA) is a common sleep disorder. Actually, literature lacks studies examining sleep, cognition, and Alzheimer's Disease (AD) cerebrospinal-fluid biomarkers in OSA patients. Therefore, we firstly studied cognitive performances, polysomnographic sleep, and CSF β-amyloid, tau proteins and lactate levels in patients affected by subjective cognitive impairment (SCI) divided in three groups: OSA patients (showing an Apnea-Hypopnea Index - AHI ≥15/h), controls (showing an AHI<15/h), and patients treating OSA by continuous positive airway pressure (CPAP)...
January 28, 2017: Sleep
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