• Barbara J Snider, Anne M Fagan, Catherine Roe, Aarti R Shah, Elizabeth A Grant, Chengjie Xiong, John C Morris, and David M Holtzman.
• Department of Neurology, Washington University School of Medicine, Campus Box 8111, 660 S Euclid, St Louis, MO 63110, USA. sniderj@neuro.wustl.edu
• Arch. Neurol. 2009 May 1; 66 (5): 638-45.

BackgroundCerebrospinal fluid (CSF) levels of Abeta peptide 1-42 (Abeta 42), tau, and phosphorylated tau (ptau) are potential biomarkers of Alzheimer disease.ObjectiveTo determine whether Abeta 42, tau, and ptau predict the rate of cognitive change in individuals with very mild dementia of the Alzheimer type (DAT).DesignRetrospective analysis of CSF biomarkers and clinical data.SettingAn academic Alzheimer disease research center.ParticipantsResearch volunteers in a longitudinal study of aging and cognition. Participants (n = 49) had a clinical diagnosis of very mild DAT with a Clinical Dementia Rating (CDR) of 0.5 at the time of lumbar puncture. All the participants had at least 1 follow-up assessment (mean [SD] follow-up, 3.5 [1.8] years).Main Outcome MeasuresBaseline CSF levels of Abeta 42, Abeta 40, tau, and ptau at threonine 181 (ptau181) and the rate of dementia progression as measured using the CDR sum of boxes (CDR-SB) score and psychometric performance.ResultsThe rate of dementia progression was significantly more rapid in individuals with lower baseline CSF Abeta 42 levels, higher tau or ptau181 levels, or high tau: Abeta 42 ratios. For example, the annual change in the CDR-SB score was 1.1 for the lowest 2 tertiles of Abeta 42 values and 0.3 for the highest tertile of Abeta 42 values.ConclusionsIn individuals with very mild DAT, lower CSF Abeta 42 levels, high tau or ptau181 levels, or high tau:Abeta 42 ratios quantitatively predict more rapid progression of cognitive deficits and dementia. Biomarkers of CSF may be useful prognostically and to identify individuals who are more likely to progress for participation in therapeutic clinical trials.

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