Affiliations: [a] Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at Göteborg University, Mölndal, Sweden | [b] Innogenetics, Ghent, Belgium
Correspondence:
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Corresponding author: Henrik Zetterberg, MD, PhD, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at Göteborg University, S-431 80 Mölndal, Sweden. Tel.: +46 31 3432377; Fax: +46 31 3432426; E-mail: henrik.zetterberg@clinchem.gu.se.
Note: [] Communicated by Giulio Pasinetti
Abstract: This study examines the intra-individual stability of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) over 2 years in 83 patients with mild cognitive impairment (MCI) and 17 cognitively healthy control individuals. All participants underwent clinical and neuropsychological evaluation and lumbar puncture at baseline and after 2 years at a university hospital memory clinic. CSF was analyzed for total tau (T-tau), phospho-tau181 (P-tau181) and amyloid-β1–42 (Aβ1–42). During the 2-year observational time, 12 MCI patients progressed to AD and 3 progressed to vascular dementia, while 68 remained stable. Baseline T-tau and P-tau181 levels were elevated in the MCI-AD group as compared to the stable MCI patients and the control group (p<0.01), while baseline Aβ1–42 levels were lower (p<0.001). Stable MCI patients were biochemically indistinguishable from controls. The biomarker levels at baseline and after 2 years showed Pearson R values between 0.81 and 0.91 (p<0.001) and coefficients of variation of 7.2 to 8.7%. In conclusion, intra-individual biomarker levels are remarkably stable over 2 years. Thus, even minor biochemical changes induced by treatment against AD should be detectable using these biomarkers, which bodes well for their usefulness as surrogate markers for drug efficacy in clinical trials.
