Association of deposition of tau and amyloid-β proteins with structural connectivity changes in cognitively normal older adults and Alzheimer's disease spectrum patients.

INTRODUCTION

Alzheimer's disease (AD) is characterized by accumulation of extracellular amyloid-β and intracellular tau neurofibrillary tangles. The recent advent of tau positron emission tomography (PET) has enabled in vivo assessment of tau pathology. The aim of this study was to explore whether tau deposition influences the structural connectivity in amyloid-negative and amyloid-positive groups, and further explore the difference between the groups.

METHODS

We investigated 18 patients with amnestic mild cognitive impairment/mild AD (AD-spectrum group) and 35 cognitively normal older adults (CN group) using diffusion MRI, amyloid, and tau PET imaging. Diffusion connectometry was performed to identify white matter pathways correlated with each of the six variables of tau deposition in the bilateral hippocampi, temporal lobes, posterior and anterior cingulate cortices, precunei, orbitofrontal lobes, and entire cerebrum.

RESULTS

The CN group showed increased connectivity along with an increased tau deposition in the bilateral hippocampi, temporal lobes, and entire cerebrum, whereas the AD-spectrum group showed decreased connectivity in the bilateral hippocampi, temporal lobes, anterior and posterior cingulate cortices, precunei, and entire cerebrum.

CONCLUSION

These findings suggest that tau deposition in the CN group seems to induce a compensatory response against early neuronal injury or chronic inflammation associated with normal aging, whereas the coexistence of amyloid and tau in the AD-spectrum group seems to outweigh the compensatory response leading to decreased connectivity, suggesting that amyloid plays a crucial role in alternating structural connectivity.