Correlation of Cerebrospinal Fluid Levels of Tau Protein Phosphorylated at Threonine 231 With Rates of Hippocampal Atrophy in Alzheimer Disease

Abstract

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.