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NEUROLOGY 2007;69:1006-1011
© 2007 American Academy of Neurology

Longitudinal changes of CSF biomarkers in memory clinic patients

F. H. Bouwman, MD, W. M. van der Flier, PhD, N.S.M. Schoonenboom, MD, E. J. van Elk, A. Kok, F. Rijmen, M. A. Blankenstein, PhD and P. Scheltens, MD, PhD

From the Alzheimer Center and Department of Neurology (F.H.B., W.M.v.d.F., N.S.M.S., P.S.), Department of Clinical Chemistry (N.S.M.S., E.J.v.E., A.K., M.A.B.), and Department of Clinical Epidemiology and Biostatistics (F.R.), VU Medical Center, Amsterdam, The Netherlands.

Address correspondence and reprint requests to Dr. Femke H. Bouwman, VU Medical Center, PO Box 7057, 1081 HV Amsterdam, The Netherlands femke.bouwman{at}vumc.nl

Objective: In Alzheimer disease (AD), longitudinal changes of beta-amyloid1-42 (Aß1-42), tau, and phosphorylated tau at threonine 181 (ptau-181) in CSF have been reported in small studies only. We evaluated the natural course of CSF biomarkers in patients with AD, subjective complaints, and mild cognitive impairment (MCI).

Methods: One hundred five patients (50 AD, 38 MCI, 17 subjective complaints) underwent two lumbar punctures, with a mean interval of 21 ± 9 months. CSF levels of Aß1-42, tau, and ptau-181 were measured.

Results: CSF Aß1-42 and tau levels showed main effects for both diagnosis and time (all p < 0.05), with average increases of 47 ± 72 and 49 ± 143 pg/mL. The interaction terms were not significant, which implies a similar time effect for all diagnostic groups. CSF ptau-181 levels showed a main effect for diagnosis (p = 0.01) but not for time (p = 0.27, increase of 1.0 ± 12 pg/mL).

Conclusion: Levels of CSF beta-amyloid1-42 and tau but not phosphorylated tau at threonine 181 increased over time in this memory clinic patient cohort with comparable change in all diagnostic groups. The cross-sectional difference between diagnostic groups, however, exceeded by far the longitudinal changes within individuals, suggesting that these biomarkers are not sensitive as markers of disease progression.

The Alzheimer Center VUMC is supported by Alzheimer Nederland and Stichting VUMC funds. The clinical database structure was developed with funding from Stichting Dioraphte.

Disclosure: The authors report no conflicts of interest.

Received August 15, 2006. Accepted in final form April 9, 2007.




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