Association of CSF total tau and phospho-tau (181) with cerebral atrophy in mild cognitive impairment and Alzheimer's disease

Objective: To examine the association of levels of total tau (t-tau) and phospho-tau (p-tau) 181 with brain morphology in mild cognitive impairment as defined by the concept of aging-associated cognitive decline (AACD) and Alzheimer's disease (AD). Method: Twenty-three subjects with AACD, 16 with AD and 15 healthy controls underwent magnetic resonance imaging and lumbar puncture. Voxel-based morphometry (VBM) was performed to investigate the association between CSF tau levels and cerebral gray matter density throughout the entire brain. Results: VBM revealed both, elevated t-tau and p-tau181 concentrations to be associated with reduced gray matter density in temporal, parietal and frontal regions. Within the AACD group, elevated CSF levels of p-tau181 (but not t-tau) were correlated with a pronounced atrophy in the right hippocampus. Conclusion: Elevated CSF levels of t-tau and p-tau181 reflect degenerative processes in AD typical cortical regions. Our findings in AACD subjects support the hypothesis that p-tau181 might be more specifically related to neurodegenerative changes in early AD.