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

Article type: Research Article

Authors: Jongbloed, Wesley^{a; b} | Bruggink, Kim A.^c | Kester, Maartje I.^b | Visser, Pieter-Jelle^{b; d} | Scheltens, Philip^b | Blankenstein, Marinus A.^a | Verbeek, Marcel M.^c | Teunissen, Charlotte E.^a | Veerhuis, Robert^{a; e; *}

Affiliations: [a] Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands | [b] Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands | [c] Department of Neurology, Department of Laboratory Medicine, Donders Institute for Brain, Cognition and behaviour, Alzheimer Centre Nijmegen, Radboud University Medical Centre, Nijmegen, The Netherlands | [d] Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, University of Maastricht, Maastricht, The Netherlands | [e] Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands

Correspondence: [*] Correspondence to: Robert Veerhuis, PhD, VU Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. Tel.: +31 20 444 3868; E-mail: r.veerhuis@vumc.nl.

Abstract: 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.

Keywords: Alzheimer's disease, amyloid-β peptides, biological markers, cerebrospinal fluid, cognition, dementia, disease progression, mild cognitive impairment

DOI: 10.3233/JAD-142136

Journal: Journal of Alzheimer's Disease, vol. 45, no. 1, pp. 35-43, 2015