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Biomarkers and Alzheimer's

Antonella Tramutola, Giulia Abate, Chiara Lanzillotta, Francesca Triani, Eugenio Barone, Federica Iavarone, Federica Vincenzoni, Massimo Castagnola, Mariagrazia Marziano, Maurizio Memo, Emirena Garrafa, D Allan Butterfield, Marzia Perluigi, Fabio Di Domenico, Daniela Uberti
Alzheimer's disease (AD) is a progressive form of dementia characterized by increased production of amyloid-β plaques and hyperphosphorylated tau protein, mitochondrial dysfunction, elevated oxidative stress, reduced protein clearance, among other. Several studies showed systemic modifications of immune and inflammatory systems due, in part, to decreased levels of CD3+ lymphocytes in peripheral blood in AD. Considering that oxidative stress, both in the brain and in the periphery, can influence the activation and differentiation of T-cells, we investigated the 3-nitrotyrosine (3-NT) proteome of blood T-cells derived from AD patients compared to non-demented (ND) subjects by using a proteomic approach...
October 12, 2018: Free Radical Biology & Medicine
Xiaochen Hu, Charlotte Teunissen, Annika Spottke, Michael T Heneka, Emrah Düzel, Oliver Peters, Siyao Li, Josef Priller, Katharina Bürger, Stefan Teipel, Christoph Laske, Sander Verfaillie, Frederik Barkhof, Nina Coll-Padrós, Lorena Rami, Jose Luis Molinuevo, Wiesje van der Flier, Frank Jessen
INTRODUCTION: Previous studies showed associations of brain volume differences and biomarker evidence for Alzheimer's disease (AD) in subjective cognitive decline (SCD). The consistency of this finding across SCD studies has not been investigated. METHODS: We studied gray matter volume differences between SCD subjects with and without cerebrospinal fluid biomarker evidence for AD across three European memory clinic samples (DZNE Longitudinal Cognitive Impairment and Dementia study, Amsterdam, Barcelona)...
October 12, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Dallas P Veitch, Michael W Weiner, 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 overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI is a multisite, longitudinal, observational study that has collected many biomarkers since 2004. Recent publications highlight the multifactorial nature of late-onset AD. We discuss selected topics that provide insights into AD progression and outline how this knowledge may improve clinical trials. METHODS: We used standard methods to identify nearly 600 publications using ADNI data from 2016 and 2017 (listed in Supplementary material and searchable at http://adni...
October 12, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Åsa Sandelius, Erik Portelius, Åsa Källén, Henrik Zetterberg, Uros Rot, Bob Olsson, Jon B Toledo, Leslie M Shaw, Virginia M Y Lee, David J Irwin, Murray Grossman, Daniel Weintraub, Alice Chen-Plotkin, David A Wolk, Leo McCluskey, Lauren Elman, Vesna Kostanjevecki, Manu Vandijck, Jennifer McBride, John Q Trojanowski, Kaj Blennow
INTRODUCTION: The level of the presynaptic protein growth-associated protein 43 (GAP-43) in cerebrospinal fluid (CSF) has previously been shown to be increased in Alzheimer's disease (AD) and thus may serve as an outcome measure in clinical trials and facilitate earlier disease detection. METHODS: We developed an enzyme-linked immunosorbent assay for CSF GAP-43 and measured healthy controls (n = 43), patients with AD (n = 275), or patients with other neurodegenerative diseases (n = 344)...
October 12, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Lisa Müller-Ehrenberg, Joost M Riphagen, Frans R J Verhey, Alexander T Sack, Heidi I L Jacobs
Measures of amyloid-β (Aβ) and phosphorylated tau (p-tau) concentrations in cerebrospinal fluid are extensively used for diagnostic and research purposes in Alzheimer's disease (AD) as correlates of cortical thinning and cognitive outcomes. The present study investigated the relationship of Aβ and p-tau with hippocampal subfield volumes Cornu Ammonis (CA) 1-4, dentate gyrus (DG), and subiculum. Subfields were segmented from T1-weighted images from the ADNI-population using FreeSurfer v6. Linear and polynomial regression models revealed distinct associations of Aβ and p-tau with subfield volumes...
October 5, 2018: Journal of Alzheimer's Disease: JAD
Mafalda Ramos de Matos, Catarina Ferreira, Sanna-Kaisa Herukka, Hilkka Soininen, André Janeiro, Isabel Santana, Inês Baldeiras, Maria Rosário Almeida, Alberto Lleó, Oriol Dols-Icardo, Daniel Alcolea, Luisa Benussi, Giuliano Binetti, Anna Paterlini, Roberta Ghidoni, Benedetta Nacmias, Olga Meulenbroek, Linda J C van Waalwijk van Doorn, H Bea Kuiperij, Lucrezia Hausner, Gunhild Waldemar, Anja Hviid Simonsen, Magda Tsolaki, Olymbia Gkatzima, Catarina Resende de Oliveira, Marcel M Verbeek, Jordi Clarimon, Mikko Hiltunen, Alexandre de Mendonça, Madalena Martins
Cerebrospinal fluid (CSF) biomarkers have been extensively investigated in the Alzheimer's disease (AD) field, and are now being applied in clinical practice. CSF amyloid-beta (Aβ1-42), total tau (t-tau), and phosphorylated tau (p-tau) reflect disease pathology, and may be used as quantitative traits for genetic analyses, fostering the identification of new genetic factors and the proposal of novel biological pathways of the disease. In patients, the concentration of CSF Aβ1-42 is decreased due to the accumulation of Aβ1-42 in amyloid plaques in the brain, while t-tau and p-tau levels are increased, indicating the extent of neuronal damage...
October 9, 2018: Journal of Alzheimer's Disease: JAD
Fanshuang Zhang, Jing Wei, Xundou Li, Chao Ma, Youhe Gao
Alzheimer's disease (AD) is an incurable age-associated neurodegenerative disorder that is characterized by irreversible progressive cognitive deficits and extensive brain damage. The identification of candidate biomarkers before amyloid-β plaque deposition occurs is therefore of great importance for the early intervention of AD. Urine, which is not regulated by homeostatic mechanisms, theoretically accumulates changes associated with AD earlier than cerebrospinal fluid and blood. In this study, an APP (swe)/PSEN1dE9 transgenic mouse model was used to identify candidate biomarkers for early AD...
October 6, 2018: Journal of Alzheimer's Disease: JAD
Samir Abu-Rumeileh, Nicola Mometto, Anna Bartoletti-Stella, Barbara Polischi, Federico Oppi, Roberto Poda, Michelangelo Stanzani-Maserati, Pietro Cortelli, Rocco Liguori, Sabina Capellari, Piero Parchi
Cerebrospinal fluid (CSF) neurofilament light chain protein (NfL) and Alzheimer's disease (AD) core biomarker levels have been evaluated in cohorts of patients with frontotemporal dementia (FTD), but the distribution of values across the different clinical syndromes and underlying proteinopathies, and the relative diagnostic accuracy appear discordant among studies. We measured cerebrospinal fluid (CSF) NfL, total (t)-tau, phosphorylated (p)-tau, and amyloid-β (Aβ)42 in healthy controls (n = 38) and subjects with a clinical, genetic, CSF biomarker-based, and/or neuropathological diagnosis of FTD (n = 141) or AD (n = 60)...
October 5, 2018: Journal of Alzheimer's Disease: JAD
Kim E Innes, Terry Kit Selfe, Kathleen Brundage, Caitlin Montgomery, Sijin Wen, Sahiti Kandati, Hannah Bowles, Dharma Singh Khalsa, Zenzi Huysmans
BACKGROUND: Telomere length (TL), telomerase activity (TA), and plasma amyloid-β (Aβ) levels have emerged as possible predictors of cognitive decline and dementia. OBJECTIVE: To assess the: 1) effects of two 12-week relaxation programs on TL, TA, and Aβ levels in adults with subjective cognitive decline; and 2) relationship of biomarker changes to those in cognitive function, psychosocial status, and quality of life (QOL). METHODS: Participants were randomized to a 12-week Kirtan Kriya meditation (KK) or music listening (ML) program and asked to practice 12 minutes/day...
October 11, 2018: Journal of Alzheimer's Disease: JAD
Marie Bruun, Hanneke F M Rhodius-Meester, Juha Koikkalainen, Marta Baroni, Le Gjerum, Afina W Lemstra, Frederik Barkhof, Anne M Remes, Timo Urhemaa, Antti Tolonen, Daniel Rueckert, Mark van Gils, Kristian S Frederiksen, Gunhild Waldemar, Philip Scheltens, Patrizia Mecocci, Hilkka Soininen, Jyrki Lötjönen, Steen G Hasselbalch, Wiesje M van der Flier
Introduction: We studied, using a data-driven approach, how different combinations of diagnostic tests contribute to the differential diagnosis of dementia. Methods: In this multicenter study, we included 356 patients with Alzheimer's disease, 87 frontotemporal dementia, 61 dementia with Lewy bodies, 38 vascular dementia, and 302 controls. We used a classifier to assess accuracy for individual performance and combinations of cognitive tests, cerebrospinal fluid biomarkers, and automated magnetic resonance imaging features for pairwise differentiation between dementia types...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Feng Feng, Pan Wang, Kun Zhao, Bo Zhou, Hongxiang Yao, Qingqing Meng, Lei Wang, Zengqiang Zhang, Yanhui Ding, Luning Wang, Ningyu An, Xi Zhang, Yong Liu
Alzheimer's disease (AD) is characterized by progressive dementia, especially in episodic memory, and amnestic mild cognitive impairment (aMCI) is associated with a high risk of developing AD. Hippocampal atrophy/shape changes are believed to be the most robust magnetic resonance imaging (MRI) markers for AD and aMCI. Radiomics, a method of texture analysis, can quantitatively examine a large set of features and has previously been successfully applied to evaluate imaging biomarkers for AD. To test whether radiomic features in the hippocampus can be employed for early classification of AD and aMCI, 1692 features from the caudal and head parts of the bilateral hippocampus were extracted from 38 AD patients, 33 aMCI patients and 45 normal controls (NCs)...
2018: Frontiers in Aging Neuroscience
Thomas Keller, Francisco R López-Picón, Anna Krzyczmonik, Sarita Forsback, Anna K Kirjavainen, Jatta S Takkinen, Obada Alzghool, Johan Rajander, Simo Teperi, Fanny Cacheux, Annelaure Damont, Frédéric Dollé, Juha O Rinne, Olof Solin, Merja Haaparanta-Solin
INTRODUCTION: Neuroinflammation is associated with several neurological disorders, including Alzheimer's disease (AD). The translocator protein 18 kDa (TSPO), due to its overexpression during microglial activation and relatively low levels in the brain under normal neurophysiological conditions, is commonly used as an in vivo biomarker for neuroinflammation. Reported here is the preclinical evaluation of [18 F]F-DPA, a promising new TSPO-specific radioligand, as a tool for the detection of activated microglia at different ages in the APP/PS1-21 mouse model of AD and a blocking study to determine the specificity of the tracer...
September 26, 2018: Nuclear Medicine and Biology
Cinzia Costa, Michele Romoli, Claudio Liguori, Lucia Farotti, Paolo Eusebi, Chiara Bedetti, Sabrina Siliquini, Elena Nardi Cesarini, Andrea Romigi, Nicola B Mercuri, Lucilla Parnetti, Paolo Calabresi
Although amyloid pathology plays a role in epilepsy, little is known about the relationship between beta amyloid and progression to Alzheimer's disease (AD) among patients with late-onset epilepsy of unknown origin (LOEU). This multicenter, observational, prospective study enrolled 40 consecutive nondemented adults diagnosed with LOEU, together with 43 age- and sex-matched healthy controls. All patients completed neuropsychological tests, core CSF AD biomarkers assessment (Aβ1-42 , total tau, and phosphorylated tau), and follow-up for a mean of 3 years to verify cognitive decline...
September 18, 2018: Neurobiology of Aging
Yuanyuan Liu, Mengying Wei, Kexin Yue, Mingxin Hu, Shizhe Li, Lihui Men, Zifeng Pi, Zhiqiang Liu, Zhongying Liu
Alzheimer's disease (AD) is a progressive neurodegenerative disorder, with no effective method for its treatment so far. The pathogenesis of AD has been reported, but the endogenous metabolic profile and disease-related biomarkers are still not clear. To better understand AD, an AD model induced by injecting β-amyloid 25-35 (Aβ 25-35) solution into bilateral hippocampus was developed on Sprague-Dawley rats. After 8 weeks of modeling, the impairment of spatial learning and memory ability in AD rats were assessed by Morris water maze task...
October 11, 2018: Neuroscience
Sun-Ho Han, Jong-Chan Park, Min Soo Byun, Dahyun Yi, Jun Ho Lee, Dong Young Lee, Inhee Mook-Jung
Cerebral β-amyloid (cAβ) deposition and cholinergic dysfunction have been considered as major pathological and functional hallmarks of Alzheimer's disease (AD). Acetylcholinesterase (AChE) is one of the major cholinergic enzymes, and there is no report to show the relationship between cAβ accumulation and peripheral AChE alteration in early stage of AD pathogenesis. Recent studies demonstrate that cAβ starts to deposit 15-20 years ahead of symptomatic appearance and this preclinical AD is important for early diagnosis of disease...
September 8, 2018: Neurobiology of Aging
Thomas K Karikari, David A Nagel, Alastair Grainger, Charlotte Clarke-Bland, Eric J Hill, Kevin G Moffat
Increasing evidence suggests that small oligomers are the principal neurotoxic species of tau in Alzheimer's disease and other tauopathies. However, mechanisms of tau oligomer-mediated neurodegeneration are poorly understood. The transience of oligomers due to aggregation can compromise the stability of oligomers prepared in vitro. Consequently, we sought to develop an efficient method which maintains the stability and globular conformation of preformed oligomers. This study demonstrates that labeling a single-cysteine form of the pro-aggregant tau four-repeat region (K18) with either Alexa Fluor 488-C5-maleimide or N-ethylmaleimide in reducing conditions stabilizes oligomers by impeding their further aggregation...
October 10, 2018: Analytical Biochemistry
Cara M Altimus, Kirstie Keller, Patrick Brannelly, Erin Ross, Chang-Ting Lin, Ekemini A U Riley, LaTese Briggs, Jeremy Smith, Melissa Stevens
Neurodegenerative diseases encompass a range of diagnoses, such as Alzheimer's disease and Parkinson's disease. Despite decades of advancements in understanding the neurobiology of individual diseases, this class has few disease-modifying therapeutics and a paucity of biomarkers for diagnosis or progression. However, tau protein aggregation has emerged as a potential unifying factor across several neurodegenerative diseases, which has prompted a rapid growth in tau-related funding. In spite of this growth, research funding in this area is not in line with the immense magnitude of disease burden, and drug discovery and clinical research remain underfunded...
October 3, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Hua Zhang, Kok Pin Ng, Joseph Therriault, Min Su Kang, Tharick A Pascoal, Pedro Rosa-Neto, Serge Gauthier
Background: Visinin-like protein-1 (VILIP-1) and chitinase-3-like protein 1 (CHI3L1 or YKL-40) in cerebrospinal fluid (CSF) are newly discovered markers indicating neuronal damage and microglial activation, respectively. Phosphorylated tau (p-tau) reflects the neuropathology of Alzheimer's disease (AD) and is useful as diagnostic markers for AD. However, it is unknown whether these biomarkers have similar or complementary information in AD. Methods: We stratified 121 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database into cognitively normal (CN), stable mild cognitive impairment (sMCI), progressive MCI (pMCI), and dementia due to AD...
2018: Translational Neurodegeneration
Hitomi Yamamoto-Imoto, Daria Zamolodchikov, Zu-Lin Chen, S Lloyd Bourne, Syeda Rizvi, Pradeep Singh, Erin H Norris, Frances Weis-Garcia, Sidney Strickland
Introduction: Accumulation of β-amyloid is a pathological hallmark of Alzheimer's disease (AD). β-Amyloid activates the plasma contact system leading to kallikrein-mediated cleavage of intact high-molecular-weight kininogen (HKi) to cleaved high-molecular-weight kininogen (HKc). Increased HKi cleavage is observed in plasma of AD patients and mouse models by Western blot. For potential diagnostic purposes, a more quantitative method that can measure HKc levels in plasma with high sensitivity and specificity is needed...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Federico Verde, Petra Steinacker, Jochen H Weishaupt, Jan Kassubek, Patrick Oeckl, Steffen Halbgebauer, Hayrettin Tumani, Christine A F von Arnim, Johannes Dorst, Emily Feneberg, Benjamin Mayer, Hans-Peter Müller, Martin Gorges, Angela Rosenbohm, Alexander E Volk, Vincenzo Silani, Albert C Ludolph, Markus Otto
OBJECTIVE: To determine the diagnostic and prognostic performance of serum neurofilament light chain (NFL) in amyotrophic lateral sclerosis (ALS). METHODS: This single-centre, prospective, longitudinal study included the following patients: 124 patients with ALS; 50 patients without neurodegenerative diseases; 44 patients with conditions included in the differential diagnosis of ALS (disease controls); 65 patients with other neurodegenerative diseases (20 with frontotemporal dementia, 20 with Alzheimer's disease, 19 with Parkinson's disease, 6 with Creutzfeldt-Jakob disease (CJD))...
October 11, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
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