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      Cerebrospinal fluid biomarkers for Alzheimer's disease in Down syndrome

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          Abstract

          Down syndrome (DS), present in nearly six million people, is associated with an extremely high risk to develop Alzheimer's disease (AD). Amyloid-β and tau pathology are omnipresent from age 40 years onward, but clinical symptoms do not appear in all DS individuals. Dementia diagnostics is complex in this population, illustrating the great need for predictive biomarkers. Although blood biomarkers have not yet proven useful, cerebrospinal fluid (CSF) biomarkers (low amyloid-β42, high t-tau, and high p-tau) effectively contribute to AD diagnoses in the general population and are increasingly used in clinical practice. Surprisingly, CSF biomarkers have been barely evaluated in DS. Breaking the taboo on CSF analyses would finally allow for the elucidation of its utility in (differential) diagnoses and staging of disease severity. A sensitive and specific biomarker profile for AD in DS would be of paramount importance to daily care, adaptive caregiving, and specific therapeutic interventions.

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          Down syndrome and Alzheimer's disease: Common pathways, common goals.

          Dean Hartley, Thomas Blumenthal, Maria Carrillo … (2015)
          In the United States, estimates indicate there are between 250,000 and 400,000 individuals with Down syndrome (DS), and nearly all will develop Alzheimer's disease (AD) pathology starting in their 30s. With the current lifespan being 55 to 60 years, approximately 70% will develop dementia, and if their life expectancy continues to increase, the number of individuals developing AD will concomitantly increase. Pathogenic and mechanistic links between DS and Alzheimer's prompted the Alzheimer's Association to partner with the Linda Crnic Institute for Down Syndrome and the Global Down Syndrome Foundation at a workshop of AD and DS experts to discuss similarities and differences, challenges, and future directions for this field. The workshop articulated a set of research priorities: (1) target identification and drug development, (2) clinical and pathological staging, (3) cognitive assessment and clinical trials, and (4) partnerships and collaborations with the ultimate goal to deliver effective disease-modifying treatments.
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            Relationship between β-Secretase, inflammation and core cerebrospinal fluid biomarkers for Alzheimer's disease.

            Daniel Alcolea, María Carmona-Iragui, Marc Suárez-Calvet … (2014)
            Biomarkers in the cerebrospinal fluid (CSF) can track specific pathophysiological pathways underlying Alzheimer's disease (AD). The connection between these biomarkers remains unclear.
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              The Dutch Parelsnoer Institute - Neurodegenerative diseases; methods, design and baseline results

              Pauline Aalten, Inez HGB Ramakers, Geert Biessels … (2014)
              Background The Parelsnoer Institute is a collaboration between 8 Dutch University Medical Centers in which clinical data and biomaterials from patients suffering from chronic diseases (so called “Pearls”) are collected according to harmonized protocols. The Pearl Neurodegenerative Diseases focuses on the role of biomarkers in the early diagnosis, differential diagnosis and in monitoring the course of neurodegenerative diseases, in particular Alzheimer’s disease. The objective of this paper is to describe the design and methods of the Pearl Neurodegenerative Diseases, as well as baseline descriptive variables, including their biomarker profile. Methods The Pearl Neurodegenerative Diseases is a 3-year follow-up study of patients referred to a memory clinic with cognitive complaints. At baseline, all patients are subjected to a standardized examination, including clinical data and biobank materials, e.g. blood samples, MRI and cerebrospinal fluid. At present, in total more than 1000 patients have been included, of which cerebrospinal fluid and DNA samples are available of 211 and 661 patients, respectively. First descriptives of a subsample of the data (n = 665) shows that patients are diagnosed with dementia (45%), mild cognitive impairment (31%), and subjective memory complaints (24%). Discussion The Pearl Neurodegenerative Diseases is an ongoing large network collecting clinical data and biomaterials of more than 1000 patients with cognitive impairments. The project has started with data analyses of the baseline characteristics and biomarkers, which will be the starting point of future specific research questions that can be answered by this unique dataset.
              Article 0 comments Cited 38 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Peter P. De Deyn
                Journal
                Journal ID (nlm-ta): Alzheimers Dement (Amst)
                Journal ID (iso-abbrev): Alzheimers Dement (Amst)
                Title: Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring
                Publisher: Elsevier
                ISSN (Electronic): 2352-8729
                Publication date PMC-release: 20 March 2017
                Publication date Collection: 2017
                Publication date (Electronic): 20 March 2017
                Volume: 8
                Pages: 1-10
                Affiliations
                [a ]Department of Neurology and Alzheimer Research Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
                [b ]Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium
                [c ]Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
                [d ]Down Medical Center, Catalan Down Syndrome Foundation, Barcelona, Spain
                Author notes
                [∗ ]Corresponding author. Tel.: +31-50-361-4650; Fax: +31-50-361-1707. p.p.de.deyn@ 123456umcg.nl
                Article
                Publisher ID: S2352-8729(17)30015-5
                DOI: 10.1016/j.dadm.2017.02.006
                PMC ID: 5384293
                PubMed ID: 28413821
                SO-VID: 69864b43-7d49-4c6b-901d-313fa48e0468
                Copyright © © 2017 The Authors
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Categories
                Subject: Cerebrospinal Fluid Biomarkers

                Keywords: alzheimer's disease,biomarkers,cerebrospinal fluid,dementia,down syndrome
                Data availability:
                Keywords: alzheimer's disease, biomarkers, cerebrospinal fluid, dementia, down syndrome

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