Association of total tau and phosphorylated tau 181 protein levels in cerebrospinal fluid with cerebral atrophy in mild cognitive impairment and Alzheimer disease

Abstract

Background: We sought to examine the association of levels of total tau (t-tau) and phosphorylated tau 181 (p-tau181) protein with brain morphology in mild cognitive impairment, as defined by the concept of aging-associated cognitive decline (AACD) and Alzheimer disease.

Methods: Twenty-three participants with AACD, 16 with Alzheimer disease and 15 healthy controls underwent magnetic resonance imaging and lumbar puncture. We performed voxel-based morphometry to investigate the association between tau levels in cerebrospinal fluid (CSF) and cerebral grey matter density throughout the entire brain.

Results: Voxel-based morphometry revealed that both elevated t-tau and p-tau181 concentrations were associated with reduced grey matter density in temporal, parietal and frontal regions. Among participants with AACD, elevated levels of p-tau181 (but not t-tau) in CSF were correlated with a pronounced atrophy in the right hippocampus.

Limitations: Our study was limited by the small sample, especially with respect to the analysis comprising the AACD subgroups. Moreover, we did not correct our voxel-based morphometry analyses for multiple dependent comparisons, therefore they harbour a risk of false-positive results.

Conclusion: Elevated levels of t-tau and p-tau181 in CSF reflect degenerative processes in the cortical regions typically affected in Alzheimer disease. Our findings in participants with AACD support the hypothesis that p-tau181 might be more specifically related to neurodegenerative changes in early Alzheimer disease.

Figures

Fig. 2: Brain regions showing significant loss of grey matter density in patients with aging-associated cognitive decline who had elevated p-tau181 levels compared with those who had normal p-tau181 levels (p < 0.001 uncorrected, extend threshold = 200 voxels).

Fig. 1: Brain regions showing significant inverse correlation between grey matter density and t-tau (left side) and p-tau181 (right side) concentrations in healthy controls, patients with aging-associated cognitive decline and patients with Alzheimer disease (p < 0.001 uncorrected, extend threshold = 200 voxels).