13
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Quantification of Butyrylcholinesterase Activity as a Sensitive and Specific Biomarker of Alzheimer’s Disease

      research-article
      a , a , a , a , a , a , b , c , *
      Journal of Alzheimer's Disease
      IOS Press
      Acetylcholinesterase, α-synucleinopathy, Alzheimer’s disease, amyloid-β, butyrylcholinesterase, tauopathies, thioflavin-S

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Amyloid-β (Aβ) plaques are a neuropathological hallmark of Alzheimer’s disease (AD); however, a significant number of cognitively normal older adults can also have Aβ plaques. Thus, distinguishing AD from cognitively normal individuals with Aβ plaques (NwAβ) based on Aβ plaque detection is challenging. It has been observed that butyrylcholinesterase (BChE) accumulates in plaques preferentially in AD. Thus, detecting BChE-associated plaques has the potential as an improved AD biomarker. We present Aβ, thioflavin-S, and BChE quantification of 26 postmortem brain tissues; AD ( n = 8), NwAβ ( n = 6), cognitively normal without plaques ( n = 8), and other common dementias including corticobasal degeneration, frontotemporal dementia with tau, dementia with Lewy bodies, and vascular dementia. Pathology burden in the orbitofrontal cortex, entorhinal cortex, amygdala, and hippocampal formation was determined and compared. The predictive value of Aβ and BChE quantification was determined, via receiver-operating characteristic plots, to evaluate their AD diagnostic performance using sensitivity, specificity, and area under curve (AUC) metrics. In general, Aβ and BChE-associated pathology were greater in AD, particularly in the orbitofrontal cortex. In this region, the largest increase (9.3-fold) was in BChE-associated pathology, observed between NwAβ and AD, due to the virtual absence of BChE-associated plaques in NwAβ brains. Furthermore, BChE did not associate with pathology of the other dementias. In this sample, BChE-associated pathology provided better diagnostic performance (AUC = 1.0, sensitivity/specificity = 100% /100%) when compared to Aβ (AUC = 0.98, 100% /85.7%). These findings highlight the predictive value of BChE as a biomarker for AD that could facilitate timely disease diagnosis and management.

          Related collections

          Most cited references64

          • Record: found
          • Abstract: found
          • Article: not found

          National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach.

          We present a practical guide for the implementation of recently revised National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease (AD). Major revisions from previous consensus criteria are: (1) recognition that AD neuropathologic changes may occur in the apparent absence of cognitive impairment, (2) an "ABC" score for AD neuropathologic change that incorporates histopathologic assessments of amyloid β deposits (A), staging of neurofibrillary tangles (B), and scoring of neuritic plaques (C), and (3) more detailed approaches for assessing commonly co-morbid conditions such as Lewy body disease, vascular brain injury, hippocampal sclerosis, and TAR DNA binding protein (TDP)-43 immunoreactive inclusions. Recommendations also are made for the minimum sampling of brain, preferred staining methods with acceptable alternatives, reporting of results, and clinico-pathologic correlations.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine.

            The clinical performance of a laboratory test can be described in terms of diagnostic accuracy, or the ability to correctly classify subjects into clinically relevant subgroups. Diagnostic accuracy refers to the quality of the information provided by the classification device and should be distinguished from the usefulness, or actual practical value, of the information. Receiver-operating characteristic (ROC) plots provide a pure index of accuracy by demonstrating the limits of a test's ability to discriminate between alternative states of health over the complete spectrum of operating conditions. Furthermore, ROC plots occupy a central or unifying position in the process of assessing and using diagnostic tools. Once the plot is generated, a user can readily go on to many other activities such as performing quantitative ROC analysis and comparisons of tests, using likelihood ratio to revise the probability of disease in individual subjects, selecting decision thresholds, using logistic-regression analysis, using discriminant-function analysis, or incorporating the tool into a clinical strategy by using decision analysis.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The cholinergic hypothesis of geriatric memory dysfunction.

              Biochemical, electrophysiological, and pharmacological evidence supporting a role for cholinergic dysfunction in age-related memory disturbances is critically reviewed. An attempt has been made to identify pseudoissues, resolve certain controversies, and clarify misconceptions that have occurred in the literature. Significant cholinergic dysfunctions occur in the aged and demented central nervous system, relationships between these changes and loss of memory exist, similar memory deficits can be artificially induced by blocking cholinergic mechanisms in young subjects, and under certain tightly controlled conditions reliable memory improvements in aged subjects can be achieved after cholinergic stimulation. Conventional attempts to reduce memory impairments in clinical trials hav not been therapeutically successful, however. Possible explanations for these disappointments are given and directions for future laboratory and clinical studies are suggested.
                Bookmark

                Author and article information

                Contributors
                Role: Handling Associate Editor
                Journal
                J Alzheimers Dis
                J. Alzheimers Dis
                JAD
                Journal of Alzheimer's Disease
                IOS Press (Nieuwe Hemweg 6B, 1013 BG Amsterdam, The Netherlands )
                1387-2877
                1875-8908
                28 April 2017
                11 May 2017
                2017
                : 58
                : 2
                : 491-505
                Affiliations
                [a ]Department of Medical Neuroscience, Dalhousie University , Halifax, NS, Canada
                [b ]Department of Medicine (Neurology and Geriatric Medicine), Dalhousie University , Halifax, NS, Canada
                [c ]Department of Chemistry and Physics, Mount Saint Vincent University , Halifax, NS, Canada
                Author notes
                [* ]Correspondence to: Sultan Darvesh, Room 1308, Camp Hill Veterans’ Memorial, 5955 Veterans’ Memorial Lane, Halifax, NS, B3H 2E1, Canada. Tel.: +1 902 473 2490; Fax: +1 902 473 7133; E-mail: sultan.darvesh@ 123456dal.ca .
                Article
                JAD170164
                10.3233/JAD-170164
                5438481
                28453492
                a464351d-d494-4969-914a-fb6b3d83da8d
                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
                : 12 March 2017
                Categories
                Research Article

                acetylcholinesterase,α-synucleinopathy,alzheimer’s disease,amyloid-β,butyrylcholinesterase,tauopathies,thioflavin-s

                Comments

                Comment on this article