CSF total and phosphorylated tau protein, regional glucose metabolism and dementia severity in Alzheimer's disease

Background and purpose: We investigated associations between severity of cognitive impairment, cerebrospinal fluid (CSF) concentrations of total-tau (t-tau) protein and tau phosphorylated at threonin 181 (p-tau(181)) and regional glucose metabolism measured with 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) in patients with probable Alzheimer's disease (AD). Methods: In 38 patients (mean age 66.5 +/- 8.0 years) with AD, Mini-Mental State Examination (MMSE) scores were evaluated and CSF levels of t-tau and p-tau(181) measured. All patients underwent an 18F-FDG-PET scan. Image analysis including correlation analysis and principal component analysis (PCA) were performed using SPM5 and VINCI. Results: Dementia severity (MMSE 21.2 +/- 4.9) correlated well with metabolic impairment especially in left hemisphere association areas that are typically affected in patients with AD (e.g. inferior parietal lobule, r = 0.512; medial temporal gyrus, r = 0.478; inferior temporal gyrus, r = 0.488; precuneus, r = 0.468; PCA: r = 0.639, F = 7.751; all P < 0.001). There were no associations between t-tau and p-tau(181) with dementia severity and only weak correlations between t-tau and cerebral glucose metabolism (superior parietal gyrus, r = -0.325, P < 0.05; precentral gyrus r = -0.418, P < 0.01; amygdala r = -0.362, P < 0.05). No correlations were found between p-tau(181) and regional hypometabolism in FDG-PET. Conclusion: MMSE and CSF t-tau represent different aspects of disease severity. Whilst MMSE is closely related to impaired cerebral glucose metabolism, CSF t-tau is less closely related and appears to be less well suited for assessment of disease progression.