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      Role of Fluid Biomarkers and PET Imaging in Early Diagnosis and its Clinical Implication in the Management of Alzheimer’s Disease

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          Abstract

          Clinical diagnosis of Alzheimer’s disease (AD) is based on symptoms; however, the challenge is to diagnose AD at the preclinical stage with the application of biomarkers and initiate early treatment (still not widely available). Currently, cerebrospinal fluid (CSF) amyloid-β 42 (Aβ 42) and tau are used in the clinical diagnosis of AD; nevertheless, blood biomarkers (Aβ 42 and tau) are less predictive. Amyloid-positron emission tomography (PET) imaging is an advancement in technology that uses approved radioactive diagnostic agents (florbetapir, flutemetamol, or florbetaben) to estimate Aβ neuritic plaque density in adults with cognitive impairment evaluated for AD and other causes of cognitive decline. There is no cure for AD to date—the disease progression cannot be stopped or reversed; approved pharmacological agents (donepezil, galantamine, and rivastigmine; memantine) provide symptomatic treatment. However, the disease-modifying therapies are promising; aducanumab and CAD106 are in phase III trials for the early stages of AD. In conclusion, core CSF biomarkers reflect pathophysiology of AD in the early and late stages; the application of approved radiotracers have potential in amyloid-PET brain imaging to detect early AD.

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          Most cited references68

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          Tau protein isoforms, phosphorylation and role in neurodegenerative disorders.

          Tau proteins belong to the family of microtubule-associated proteins. They are mainly expressed in neurons where they play an important role in the assembly of tubulin monomers into microtubules to constitute the neuronal microtubules network. Microtubules are involved in maintaining the cell shape and serve as tracks for axonal transport. Tau proteins also establish some links between microtubules and other cytoskeletal elements or proteins. Tau proteins are translated from a single gene located on chromosome 17. Their expression is developmentally regulated by an alternative splicing mechanism and six different isoforms exist in the human adult brain. Tau proteins are the major constituents of intraneuronal and glial fibrillar lesions described in Alzheimer's disease and numerous neurodegenerative disorders referred to as 'tauopathies'. Molecular analysis has revealed that an abnormal phosphorylation might be one of the important events in the process leading to their aggregation. Moreover, a specific set of pathological tau proteins exhibiting a typical biochemical pattern, and a different regional and laminar distribution could characterize each of these disorders. Finally, a direct correlation has been established between the progressive involvement of the neocortical areas and the increasing severity of dementia, suggesting that pathological tau proteins are reliable marker of the neurodegenerative process. The recent discovery of tau gene mutations in frontotemporal dementia with parkinsonism linked to chromosome 17 has reinforced the predominant role attributed to tau proteins in the pathogenesis of neurodegenerative disorders, and underlined the fact that distinct sets of tau isoforms expressed in different neuronal populations could lead to different pathologies.
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            High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis

            We examined whether plasma β-amyloid (Aβ)42/Aβ40, as measured by a high-precision assay, accurately diagnosed brain amyloidosis using amyloid PET or CSF p-tau181/Aβ42 as reference standards.
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              Apolipoprotein E Genotype and Sex Risk Factors for Alzheimer Disease

              It is unclear whether female carriers of the apolipoprotein E (APOE) ε4 allele are at greater risk of developing Alzheimer disease (AD) than men, and the sex-dependent association of mild cognitive impairment (MCI) and APOE has not been established.
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                Author and article information

                Journal
                J Alzheimers Dis Rep
                J Alzheimers Dis Rep
                ADR
                Journal of Alzheimer's Disease Reports
                IOS Press (Nieuwe Hemweg 6B, 1013 BG Amsterdam, The Netherlands )
                2542-4823
                30 January 2020
                12 February 2020
                2020
                : 4
                : 1
                : 21-37
                Affiliations
                [a ]Department of Neurology, National Neuroscience Institute , Singapore General Hospital, Singapore
                [b ]Duke NUS Medical School , Singapore
                [c ]Department of Neurology, Neurological Institute , Taipei Veterans General Hospital, Taipei, Taiwan
                [d ]Faculty of Medicine, National Yang-Ming University School of Medicine , Taipei, Taiwan
                [e ]Division of Neurology, Faculty of Medicine, Siriraj Hospital, Mahidol University , Bangkok, Thailand
                [f ]Faculty of Medicine, University Kula Lumpur , Royal College of Medicine Perak, Ipoh, Malaysia
                [g ]Clinical Research Centre , Hospital Seberang Jaya, Penang, Malaysia
                [h ]Department of Medicine, Hospital Seberang Jaya , Penang, Malaysia
                [i ]Institute for Neurosciences, St. Luke’s Medical Center , Metro Manila, Philippines
                [j ]Department of Neurology and Cognitive Disorders and Dementia Center, Institute of Convergence Bio-Health, Dong-A University College of Medicine , Busan, Republic of Korea
                [k ]Novartis Healthcare Private Limited, Hyderabad, India
                [l ]Novartis (Singapore) Pte. Ltd., Singapore, Singapore
                Author notes
                [* ]Correspondence to: Shahul Hameed, National Neuroscience Institute, Department of Neurology, Singapore General Hospital, Outram Road, Singapore, Singapore. E-mail: shahul.hameed@ 123456singhealth.com.sg .
                Article
                ADR190143
                10.3233/ADR-190143
                7081089
                32206755
                2b484313-72fc-4c83-81ca-9b79ab8edf5a
                © 2020 – IOS Press and the authors. All rights reserved

                This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 03 January 2020
                Categories
                Review

                alzheimer’s disease,biomarker,blood,cerebrospinal fluid,early diagnosis,positron emission tomography

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