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Harald Hampel, MD; Katharina Bürger, MD; Jens C. Pruessner, PhD; Raymond Zinkowski, PhD; John DeBernardis, PhD; Daniel Kerkman, PhD; Gerda Leinsinger, MD; Alan C. Evans, PhD; Peter Davies, PhD; Hans-Jürgen Möller, MD; Stefan J. Teipel, MD

Arch Neurol. 2005;62:770-773.

Background  The microtubule-associated tau protein abnormally phosphorylated at threonine 231 (p-tau₂₃₁) has been investigated as a potential marker of Alzheimer disease. Levels of cerebrospinal fluid (CSF) p-tau₂₃₁ vary across patients with Alzheimer disease. We hypothesized that these variations partially reflect differences in the degree of neuronal damage and therefore may be used to predict structural disease progression.

Objective  To investigate whether CSF p-tau₂₃₁ levels correlate with rates of hippocampal atrophy as an in vivo marker of regional neuronal loss.

Design and Patients  We measured hippocampal volumes on the basis of serial magnetic resonance image examinations in 22 patients with Alzheimer disease. In addition, we determined CSF p-tau₂₃₁ levels at baseline.

Results  Levels of CSF p-tau₂₃₁ were significantly correlated with baseline hippocampal volumes (P<.001) and rates of hippocampal atrophy (left hippocampus, P<.001; right hippocampus, P = .02), independent of disease duration and severity.

Conclusion  These findings suggest that variations in p-tau₂₃₁ levels may be used to predict progression of brain atrophy in patients with Alzheimer disease.

Author Affiliations: Alzheimer Memorial Center and Geriatric Psychiatry Branch, Dementia and Neuroimaging Section, Department of Psychiatry (Drs Hampel, Bürger, Pruessner, Möller, and Teipel), and Department of Radiology (Dr Leinsinger), Ludwig-Maximilian University, Munich, Germany; Applied Neurosolutions Inc, Vernon Hills, Ill (Drs Zinkowski, DeBernardis, and Kerkman); McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec (Drs Pruessner and Evans); and Department of Pathology, Albert Einstein College of Medicine, Bronx, NY (Dr Davies).

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