The Cerebrospinal Fluid Amyloid β42/40 Ratio in the Differentiation of Alzheimers Disease from Non-Alzheimers Dementia
P.E. Spies, D. Slats, J.M.C. Sjogren, B.P.H. Kremer, F.R.J. Verhey, M.G.M. Olde Rikkert and M.M. Verbeek
Affiliation: Department of Geriatric Medicine, 925, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Background: Amyloid β40 (Aβ40) is the most abundant Aβ peptide in the brain. The cerebrospinal fluid (CSF) level of Aβ40 might therefore be considered to most closely reflect the total Aβ load in the brain. Both in Alzheimers disease (AD) and in normal aging the Aβ load in the brain has a large inter-individual variability. Relating Aβ42 to Aβ40 levels might consequently provide a more valid measure for reflecting the change in Aβ metabolism in dementia patients than the CSF Aβ42 concentrations alone. This measure may also improve differential diagnosis between AD and other dementia syndromes, such as vascular dementia (VaD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). Objective: To investigate the diagnostic value of the CSF Aβ42/Aβ40 ratio in differentiating AD from controls, VaD, DLB and FTD. Methods: We analysed the CSF Aβ42/Aβ40 ratio, phosphorylated tau181 and total tau in 69 patients with AD, 26 patients with VaD, 16 patients with DLB, 27 patients with FTD, and 47 controls. Results: Mean Aβ40 levels were 2850 pg/ml in VaD and 2830 pg/ml in DLB patients, both significantly lower than in AD patients (3698 pg/ml; p < 0.01). Aβ40 levels in AD patients were not significantly different from those in controls (4035 pg/ml; p=0.384). The Aβ42/Aβ40 ratio was significantly lower in AD patients than in all other groups (p < 0.001, ANCOVA). Differentiating AD from VaD, DLB and non-AD dementia improved when the Aβ42/Aβ40 ratio was used instead of Aβ42 concentrations alone (p < 0.01) The Aβ42/Aβ40 ratio performed equally well as the combination of Aβ42, phosphorylated tau181 and total tau in differentiating AD from FTD and non-AD dementia. The diagnostic performance of the latter combination was not improved when the Aβ42/Aβ40 ratio was used instead of Aβ42 alone. Conclusion: The CSF Aβ42/Aβ40 ratio improves differentiation of AD patients from VaD, DLB and non-AD dementia patients, when compared to Aβ42 alone, and is a more easily interpretable alternative to the combination of Aβ42, p-tau and t-tau when differentiating AD from either FTD or non-AD dementia.
Keywords: Abeta40 protein, Aβ42/Aβ40 ratio, Alzheimer's disease, vascular dementia, dementia with Lewy bodies
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