Wesley Jongbloed1, Kim A Bruggink2, Maartje I Kester3, Pieter-Jelle Visser4, Philip Scheltens3, Marinus A Blankenstein5, Marcel M Verbeek2, Charlotte E Teunissen5, Robert Veerhuis6. 1. Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. 2. Department of Neurology, Department of Laboratory Medicine, Donders Institute for Brain, Cognition and behaviour, Alzheimer Centre Nijmegen, Radboud University Medical Centre, Nijmegen, The Netherlands. 3. Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. 4. Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, University of Maastricht, Maastricht, The Netherlands. 5. Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. 6. Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.
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.
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 ADpatients 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 ADpatients 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 ADpatients. 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.
Authors: Andrew A George; Jaime M Vieira; Cameron Xavier-Jackson; Michael T Gee; John R Cirrito; Heather A Bimonte-Nelson; Marina R Picciotto; Ronald J Lukas; Paul Whiteaker Journal: J Neurosci Date: 2020-11-25 Impact factor: 6.167