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Non-linear relationships of cerebrospinal fluid biomarker levels with cognitive function: an observational study

Jonathan H Williams1*, Gordon K Wilcock1, Jeffrey Seeburger2, Aimee Dallob3, Omar Laterza3, William Potter2 and A David Smith1

Author Affiliations

1 OPTIMA, University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK

2 Clinical Neuroscience and Ophthalmology, Merck Research Laboratories, 351 N. Sumneytown Pike, North Wales, PA 19454, USA

3 Clinical Development Laboratory, Merck Research Laboratories, 126 East Lincoln Avenue, Rahway, NJ 07065, USA

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Alzheimer's Research & Therapy 2011, 3:5  doi:10.1186/alzrt64

Published: 17 February 2011



Levels of cerebrospinal fluid (CSF) β-amyloid (Aβ) and Tau proteins change in Alzheimer's disease (AD). We tested if the relationships of these biomarkers with cognitive impairment are linear or non-linear.


We assessed cognitive function and assayed CSF Aβ and Tau biomarkers in 95 non-demented volunteers and 97 AD patients. We then tested non-linearities in their inter-relations.


CSF biomarkers related to cognitive function in the non-demented range of cognition, but these relations were weak or absent in the patient range; Aβ1-40's relationship was biphasic.


Major biomarker changes precede clinical AD and index cognitive impairment in AD poorly, if at all.