Amyloid beta binding partners in the brain tissue of older adults.

INTRODUCTION

The mechanism linking extracellular amyloid beta (Aβ) with intraneuronal tau tangles, pathological hallmarks of Alzheimer's disease (AD), is not understood; it was tested in the current study through Aβ binding partners.

METHODS

Data were from decedents of community-based clinical-pathological studies. Of 52 Aβ binding partners, suggested by non-human studies, levels of 34 together with total Aβ protein were quantified in the dorsolateral prefrontal cortex. Post mortem pathological assessment immunohistochemically quantified Aβ load and tau tangle density.

RESULTS

The strongest mediations between Aβ and tau tangles were observed for Ras-related C3 botulinum toxin substrate 1 (RAC1) and sodium/potassium-transporting ATPase subunit alpha-3 (ATP1A3), which collectively mediated 10.1% of the association between Aβ and tau tangles. In contrast, Aβ mediated >70% of the associations of matrix proteins with tau tangles.

DISCUSSION: Identification of Aβ binding partners that mediate the association between Aβ and tau tangles may provide new targets for AD treatment.

HIGHLIGHTS: RAC1 linked Aβ with tau tangles. ATP1A3 linked Aβ with tau. RAC1 and ATP1A3 collectively mediated 10.1% of the association between Aβ and tau. Aβ mediated >70% of the associations of matrix proteins, such as APOE, with tau.