19
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Association between increased levels of amyloid-β oligomers in plasma and episodic memory loss in Alzheimer’s disease

      research-article

      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

          Objective

          The objectives of this study were to investigate whether the plasma levels of oligomeric amyloid-β (OAβ) were affected in Alzheimer’s disease (AD) and to examine the associations (or possible correlations) between plasma OAβ levels and memory performance.

          Method

          Thirty subjects with AD and 28 cognitively normal controls were recruited in the study. The multimer detection system (MDS) was used to measure the levels of OAβ in the plasma. In addition to assessing the general cognitive function with the Mini-Mental State Examination (MMSE), Cognitive Abilities Screening Instrument (CASI), and Alzheimer’s Disease Assessment Scale–cognitive portion (ADAS-Cog), the common objects memory test (COMT) was used to examine the episodic memory performance. Pearson’s and partial correlation analyses were conducted to explore the associations between cognitive performance and OAβ levels in the plasma. A receiving operating curve (ROC) analysis was used to discriminate between the AD and control groups.

          Results

          The plasma OAβ levels in the AD group were significantly higher than those in the control group [1.88 (0.38) ng/ml vs 1.20 (0.40) ng/ml, p < 0.001]. The elevated levels of plasma OAβ showed a strong correlation with cognitive performance in patients with AD, including an inverse correlation with scores on the MMSE ( r = − 0.43, p = 0.02), CASI ( r = − 0.56, p < 0.01), and the immediate recall ( r = − 0.45, p = 0.01), 5-min delayed recall ( r = − 0.56, p < 0.01), and 30-min delayed recall ( r = − 0.71, p < 0.001) tests of the COMT, and a positive correlation with the ADAS-Cog scores ( r = 0.59, p < 0.001). The EDTA plasma Aβ oligomer optical density (OD) value measured using the MDS could discriminate between the AD and control groups with an area under the curve (AUC) of 0.89. The optimal sensitivity and specificity were 82.1% and 90.0%, respectively.

          Conclusion

          The elevated levels of OAβ in the plasma distinguished the AD and control groups and were associated with the severity of symptoms, especially memory performance, in patients with AD. Our results suggested that plasma OAβ could potentially be a simple and non-invasive blood-based biomarker for AD diagnosis. Furthermore, longitudinal studies are warranted to explore the application of plasma OAβ levels as a valid diagnostic biomarker in patients with AD.

          Electronic supplementary material

          The online version of this article (10.1186/s13195-019-0535-7) contains supplementary material, which is available to authorized users.

          Related collections

          Most cited references20

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

          Soluble fibrillar oligomer levels are elevated in Alzheimer's disease brain and correlate with cognitive dysfunction.

          Recent evidence has suggested a role for soluble oligomeric Abeta species in the pathology of Alzheimer's disease (AD). Fibrillar plaque deposits are present in non-demented individuals and levels of soluble Abeta correlate better with cognitive dysfunction in AD and transgenic mouse models. We have previously reported that there are at least two conformationally distinct types of Abeta oligomers: prefibrillar oligomers that are kinetic intermediates in fibril assembly reactions and are specifically recognized by A11 antibody and fibrillar oligomers that may represent fibril seeds or small pieces of fibrils and are recognized by a fibril specific antibody, OC. We have examined the levels of these two types of oligomers in the PBS soluble fraction of brain tissue from control cases, cases with senile degenerative changes (SDC) and AD patients. We found that the levels of soluble fibrillar oligomers detected by OC antibody are significantly elevated in multiple brain regions of AD patients. The elevated fibrillar oligomer levels were found not to be an artifact of tissue homogenization, nor a result of increased Abeta or APP levels. The concentration of fibrillar oligomers in adjacent brain regions of the same patient can vary widely and were not detected in post-mortem cerebrospinal fluid. In contrast, the level of prefibrillar oligomers are variable in both AD and age matched controls, indicating that they are not correlated with cognitive dysfunction and suggesting that they precede dementia in AD. Significant correlations were found between the levels of fibrillar oligomers and cognitive decline (MMSE scores) as well as the neuropathological hallmarks of AD. These results indicate that fibrillar oligomers may play a key role in the pathology of AD and may be a new target for diagnostic and therapeutic development.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Cognitive impairment 18 years before clinical diagnosis of Alzheimer disease dementia.

            To examine the relation of performance on brief cognitive tests to development of clinically diagnosed Alzheimer disease (AD) dementia over the following 18 years in a sample of African Americans and European Americans.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              High-molecular-weight beta-amyloid oligomers are elevated in cerebrospinal fluid of Alzheimer patients.

              There is accumulating evidence that soluble amyloid-beta (Abeta) oligomers, rather than amyloid fibrils, are the principal pathogenic species in Alzheimer disease (AD). Here, we have developed a novel enzyme-linked immunosorbent assay (ELISA) specific for high-molecular-weight (HMW) Abeta oligomers. Analysis of Abeta oligomers derived from synthetic Abeta 1-42, by size-exclusion chromatography (SEC), revealed that our ELISA specifically detected HMW Abeta oligomers of 40-200 kDa. Using this ELISA, we detected significantly higher (P<0.0001) signals in cerebrospinal fluid (CSF) samples from 25 patients with AD or mild cognitive impairment (MCI), compared to 25 age-matched controls. As a test for discriminating between the AD/MCI and control groups, the area under the curve in receiver operating characteristic analysis for the CSF HMW Abeta oligomers was greater than that for CSF Abeta x-42. Furthermore, the CSF levels of HMW Abeta oligomers showed a negative correlation with Mini-Mental State Examination scores in the AD/MCI group. We conclude that the CSF HMW Abeta oligomers detected by our ELISA could be useful as a diagnostic marker for AD, and also as a potential surrogate marker for disease severity. Our results support the idea that soluble HMW Abeta oligomers play a critical role in the pathogenesis and progression of AD.
                Bookmark

                Author and article information

                Contributors
                mengxue@bjmu.edu.cn
                litao1027@sina.com
                miriamyoung@126.com
                lxz120300@163.com
                sunzhiyu123@qq.com
                zhangjichun@pku.edu.cn
                sfsilence@126.com
                kang.sungmin@peoplebio.net
                neuroksy@snu.ac.kr
                seongaan@gachon.ac.kr
                yuxin@bjmu.edu.cn
                czhang@ccmu.edu.cn
                huali_wang@bjmu.edu.cn
                Journal
                Alzheimers Res Ther
                Alzheimers Res Ther
                Alzheimer's Research & Therapy
                BioMed Central (London )
                1758-9193
                25 October 2019
                25 October 2019
                2019
                : 11
                : 89
                Affiliations
                [1 ]ISNI 0000 0001 2256 9319, GRID grid.11135.37, Dementia Care and Research Center, Beijing Key Laboratory for Translational Research on Diagnosis and Treatment of Dementia, , Peking University Institute of Mental Health (Sixth Hospital), ; Beijing, 100191 China
                [2 ]National Clinical Research Center for Mental Disorders, Key Laboratory for Mental Health, National Health Commission, Beijing, 100191 China
                [3 ]ISNI 0000 0001 2256 9319, GRID grid.11135.37, State Key Laboratory of Membrane Biology, School of Life Sciences, PKU-IDG/McGovern Institute for Brain Research, , Peking University, ; Beijing, 100871 China
                [4 ]GRID grid.497713.f, Department of Research and Development, , PeopleBio, Inc., ; Seongnam-si, Gyeonggi-do Republic of Korea
                [5 ]Department of Neurology, Seoul National University Bundang Hospital and Seoul National University College of Medicine, 82, Gumi-ro 173, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707 Republic of Korea
                [6 ]ISNI 0000 0004 0647 2973, GRID grid.256155.0, Department of Bionano Technology, , Gachon University, ; Sujeong-gu, Seongnam-si, Gyeonggi-do 461-701 Republic of Korea
                Author information
                http://orcid.org/0000-0002-3213-6493
                Article
                535
                10.1186/s13195-019-0535-7
                6814096
                31651358
                552ba5a1-9f9c-4fa4-be8a-bfcc7ff7a4fc
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 1 June 2019
                : 26 August 2019
                Funding
                Funded by: Ministry of Science and Technology of China
                Award ID: 2017YFC1311100
                Award Recipient :
                Funded by: Beijing Municipal Science and Technology Commission
                Award ID: Z161100000516001
                Award ID: Z161100002616021
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

                Neurology
                alzheimer’s disease,amyloid oligomers,plasma,episodic memory
                Neurology
                alzheimer’s disease, amyloid oligomers, plasma, episodic memory

                Comments

                Comment on this article