CSF biomarkers of neuroinflammation in distinct forms and subtypes of neurodegenerative dementia.
Samir Abu-Rumeileh,Petra Steinacker,Barbara Polischi,Angela Mammana,Anna Bartoletti-Stella,Patrick Oeckl,Simone Baiardi,Corrado Zenesini,André Huss,Pietro Cortelli,Sabina Capellari,Markus Otto,Piero Parchi +12 more
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TLDR
CSF glial markers of neuroinflammation demonstrate limited diagnostic value but have some potential for monitoring the clinical and, possibly, preclinical phases of NDs.Abstract:
In neurodegenerative dementias (NDs) such as prion disease, Alzheimer’s disease (AD), and frontotemporal lobar degeneration (FTLD), protein misfolding leads to the tissue deposition of protein aggregates which, in turn, trigger neuroinflammation and neurodegeneration. Cerebrospinal fluid (CSF) biomarkers have the potential to reflect different aspects of these phenomena across distinct clinicopathological subtypes and disease stages. We investigated CSF glial markers, namely chitotriosidase 1 (CHIT1), chitinase-3-like protein 1 (YKL-40) and glial fibrillary acidic protein (GFAP) in prion disease subtypes (n = 101), AD (n = 40), clinicopathological subgroups of FTLD (n = 72), and controls (n = 40) using validated, commercially available ELISA assays. We explored glial biomarker levels’ associations with disease variables and neurodegenerative CSF biomarkers and evaluated their diagnostic accuracy. The genotype of the CHIT1 rs3831317 polymorphic site was also analyzed. Each ND group showed increased levels of CHIT1, YKL-40, and GFAP compared to controls with a difference between prion disease and AD or FTLD limited to YKL-40, which showed higher values in the former group. CHIT1 levels were reduced in both heterozygotes and homozygotes for the CHIT1 24-bp duplication (rs3831317) in FTLD and controls, but this effect was less significant in AD and prion disease. After stratification according to molecular subgroups, we demonstrated (i) an upregulation of all glial markers in Creutzfeldt-Jakob disease VV2 compared to other disease subtypes, (ii) a difference in CHIT1 levels between FTLD with TAU and TDP43 pathology, and (iii) a marked increase of YKL-40 in FTLD with amyotrophic lateral sclerosis (ALS) in comparison with FTLD without ALS. In prion disease, glial markers correlated with disease stage and were already elevated in one pre-symptomatic case of Gerstmann-Straussler-Scheinker disease. Regarding the diagnostic value, YKL-40 was the only glial marker that showed a moderate accuracy in the distinction between controls and NDs. NDs share a CSF profile characterized by increased levels of CSF CHIT1, YKL-40, and GFAP, which likely reflects a common neuroinflammatory response to protein misfolding and aggregation. CSF glial markers of neuroinflammation demonstrate limited diagnostic value but have some potential for monitoring the clinical and, possibly, preclinical phases of NDs.read more
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Differences Between Plasma and Cerebrospinal Fluid Glial Fibrillary Acidic Protein Levels Across the Alzheimer Disease Continuum.
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TL;DR: The authors in this paper evaluated GFAP levels throughout the entire AD continuum, from preclinical AD to AD dementia, compared with CSF GFAP, and found that GFAP magnitude changes were consistently higher among individuals in symptomatic stages of the AD continuum.
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Combination of plasma amyloid beta (1-42/1-40) and glial fibrillary acidic protein strongly associates with cerebral amyloid pathology
Inge M.W. Verberk,Elisabeth H. Thijssen,Jannet Koelewijn,Kimberley Mauroo,Jeroen Vanbrabant,Arno de Wilde,Marissa D. Zwan,Sander C.J. Verfaillie,Rik Ossenkoppele,Rik Ossenkoppele,Frederik Barkhof,Bart N.M. van Berckel,Philip Scheltens,Wiesje M. van der Flier,Erik Stoops,Hugo Vanderstichele,Charlotte E. Teunissen +16 more
TL;DR: Combination of plasma Abeta(1-42/1-40) and GFAP provides a valuable tool for the identification of amyloid PET status and associate with various disease severity measures suggesting potential for disease monitoring.
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Blood GFAP as an emerging biomarker in brain and spinal cord disorders
Ahmed Abdelhak,Matteo Foschi,Samir Abu-Rumeileh,John K. Yue,Lucio D'Anna,André Huss,Patrick Oeckl,Albert C. Ludolph,Jens Kuhle,Axel Petzold,Geoffrey T. Manley,Ari J. Green,Markus Otto,Hayrettin Tumani +13 more
TL;DR: A systematic overview of the evidence regarding the utility of blood GFAP as a biomarker in neurological diseases is provided in this article , where the authors propose a model for GFAP concentration dynamics in different conditions and discuss the limitations that hamper the widespread use of GFAP in the clinical setting.
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Plasma glial fibrillary acidic protein detects Alzheimer pathology and predicts future conversion to Alzheimer dementia in patients with mild cognitive impairment
Claudia Cicognola,Shorena Janelidze,Joakim Hertze,Henrik Zetterberg,Kaj Blennow,Kaj Blennow,Niklas Mattsson-Carlgren,Oskar Hansson +7 more
TL;DR: In this article, the ability of plasma GFAP to detect Alzheimer's disease (AD) pathology in the form of AD-related amyloid-β (Aβ) pathology and conversion to AD dementia in a mild cognitive impairment (MCI) cohort was assessed.
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Fluid biomarkers in frontotemporal dementia: past, present and future.
Imogen Swift,Aitana Sogorb-Esteve,Aitana Sogorb-Esteve,Carolin Heller,Matthis Synofzik,Matthis Synofzik,Markus Otto,Caroline Graff,Daniela Galimberti,Emily Todd,Amanda Heslegrave,Emma L. van der Ende,John C. van Swieten,Henrik Zetterberg,Jonathan D. Rohrer +14 more
TL;DR: There is much still to learn in the fluid biomarker field in FTD, but the creation of large multinational cohorts is facilitating better powered studies and will pave the way for larger omics studies, including proteomics, metabolomics and lipidomics, as well as investigations of multimodal biomarker combinations across fluids, brain imaging and other domains.
References
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Journal ArticleDOI
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Maria Luisa Gorno-Tempini,Maria Luisa Gorno-Tempini,Argye E. Hillis,Sandra Weintraub,Andrew Kertesz,Mario F. Mendez,Stefano F. Cappa,J. M. Ogar,Jonathan D. Rohrer,Sandra E. Black,Bradley F. Boeve,Facundo Manes,Nina F. Dronkers,Rik Vandenberghe,Katya Rascovsky,Karalyn Patterson,Bruce L. Miller,D. S. Knopman,John R. Hodges,M.-Marsel Mesulam,Murray Grossman +20 more
TL;DR: This article provides a classification of primary progressive aphasia (PPA) and its 3 main variants to improve the uniformity of case reporting and the reliability of research results.
Journal ArticleDOI
Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria
Bruno Dubois,Bruno Dubois,Howard Feldman,Claudia Jacova,Harald Hampel,Harald Hampel,José Luis Molinuevo,Kaj Blennow,Steven T. DeKosky,Serge Gauthier,Dennis J. Selkoe,Randall J. Bateman,Stefano F. Cappa,Sebastian J. Crutch,Sebastiaan Engelborghs,Giovanni B. Frisoni,Nick C. Fox,Douglas Galasko,Marie-Odile Habert,Gregory A. Jicha,Agneta Nordberg,Florence Pasquier,Gil D. Rabinovici,Philippe Robert,Christopher C. Rowe,Stephen Salloway,Marie Sarazin,Stéphane Epelbaum,Stéphane Epelbaum,Leonardo Cruz de Souza,Leonardo Cruz de Souza,Leonardo Cruz de Souza,Bruno Vellas,Pieter Jelle Visser,Lon S. Schneider,Yaakov Stern,Philip Scheltens,Jeffrey L. Cummings +37 more
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Bradley T. Hyman,Creighton H. Phelps,Thomas G. Beach,Eileen H. Bigio,Nigel J. Cairns,Maria C. Carrillo,Dennis W. Dickson,Charles Duyckaerts,Matthew P. Frosch,Eliezer Masliah,Suzanne S. Mirra,Peter T. Nelson,Julie A. Schneider,Dietmar Rudolf Thal,Bill Thies,John Q. Trojanowski,Harry V. Vinters,Thomas J. Montine +17 more
TL;DR: The new guidelines recognize the pre‐clinical stage of AD, enhance the assessment of AD to include amyloid accumulation as well as neurofibrillary change and neuritic plaques, and establish protocols for the neuropathologic assessment of Lewy body disease, vascular brain injury, hippocampal sclerosis, and TDP‐43 inclusions.
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