Amyloid-beta Oligomers Relate to Cognitive Decline in Alzheimer's Disease

W. Jongbloed, K.A. Bruggink, M.I. Kester, P.J. Visser, P. Scheltens, M.A. Blankenstein, M.M. Verbeek, C.E. Teunissen, R. Veerhuis

    Research output: Contribution to JournalArticleAcademicpeer-review


    Background: Amyloid-β (Aβ)-oligomers are neurotoxic isoforms of Aβ and are a potential diagnostic biomarker for Alzheimer's disease (AD). Objectives: 1) Analyze the potential of Aβ-oligomer concentrations in cerebrospinal fluid (CSF) to diagnose and predict progression to AD in a large clinical study sample. 2) Monitor Aβ-oligomer concentrations over-time, both in early and advanced stages of AD. 3) Examine the relation between Aβ-oligomer levels in CSF and cognitive functioning. Methods: 24 non-demented, 61 mild cognitive impairment (MCI), and 64 AD patients who underwent lumbar puncture and cognitive testing at baseline and follow-up were selected from the memory clinic based Amsterdam Dementia Cohort. CSF samples were analyzed for standard AD-biomarkers and Aβ-oligomer levels using a validated in-house Aβ-oligomer specific enzyme-linked immunosorbent assay. Aβ-oligomer levels were analyzed as indicators of disease progression (follow-up AD diagnosis) and cognitive decline, respectively. Results: Patient groups did not differ in Aβ-oligomer concentrations at baseline or follow-up. Baseline CSF Aβ-oligomer levels were similar in MCI patients that develop AD as in stable MCI patients. MCI and AD patients showed an annual decrease in Aβ-oligomer levels of 9.4% and 6.8%, respectively. A decrease in Aβ-oligomer levels over time was strongly associated with more severe cognitive decline in AD patients. Conclusion: Despite the limited diagnostic potential of Aβ-oligomer levels in CSF to differentiate between patient groups, and between MCI-AD and MCI-stable patients, changes in CSF Aβ-oligomer levels were related to cognitive decline. Therefore, CSF Aβ-oligomers may aid in the selection of patients with a more aggressive disease course.
    Original languageEnglish
    Pages (from-to)35-43
    JournalJournal of Alzheimer's Disease
    Issue number1
    Publication statusPublished - 2015


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