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‐tau₁₈₁) 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‐tau₁₈₁ 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‐tau₁₈₁ 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‐tau₁₈₁ 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.