Amyloid-beta Oligomers Relate to Cognitive Decline in Alzheimer's Disease
SourceJournal of Alzheimer's Disease, 45, 1, (2015), pp. 35-43
Article / Letter to editor
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Journal of Alzheimer's Disease
SubjectRadboudumc 3: Disorders of movement DCMN: Donders Center for Medical Neuroscience
BACKGROUND: Amyloid-beta (Abeta)-oligomers are neurotoxic isoforms of Abeta and are a potential diagnostic biomarker for Alzheimer's disease (AD). OBJECTIVES: 1) Analyze the potential of Abeta-oligomer concentrations in cerebrospinal fluid (CSF) to diagnose and predict progression to AD in a large clinical study sample. 2) Monitor Abeta-oligomer concentrations over-time, both in early and advanced stages of AD. 3) Examine the relation between Abeta-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 Abeta-oligomer levels using a validated in-house Abeta-oligomer specific enzyme-linked immunosorbent assay. Abeta-oligomer levels were analyzed as indicators of disease progression (follow-up AD diagnosis) and cognitive decline, respectively. RESULTS: Patient groups did not differ in Abeta-oligomer concentrations at baseline or follow-up. Baseline CSF Abeta-oligomer levels were similar in MCI patients that develop AD as in stable MCI patients. MCI and AD patients showed an annual decrease in Abeta-oligomer levels of 9.4% and 6.8%, respectively. A decrease in Abeta-oligomer levels over time was strongly associated with more severe cognitive decline in AD patients. CONCLUSION: Despite the limited diagnostic potential of Abeta-oligomer levels in CSF to differentiate between patient groups, and between MCI-AD and MCI-stable patients, changes in CSF Abeta-oligomer levels were related to cognitive decline. Therefore, CSF Abeta-oligomers may aid in the selection of patients with a more aggressive disease course.
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