Alzheimer’s Resarch and Therapy | January 4, 2021

Su Q, Li T, He PF, Lu XC, Yu Q, Gao QC, Wang ZJ, Wu MN, Yang D and Qi JS

Alzheimers Res Ther. 2021;13:7

DOI: https://doi.org/10.1186/s13195-020-00746-8

This study was peformed using a Simoa® Homebrew assay.

Abstract

Background

Alzheimer’s disease (AD) is an intractable neurodegenerative disorder in the elderly population, currently lacking a cure. Trichostatin A (TSA), a histone deacetylase inhibitor, showed some neuroprotective roles, but its pathology-improvement effects in AD are still uncertain, and the underlying mechanisms remain to be elucidated. The present study aims to examine the anti-AD effects of TSA, particularly investigating its underlying cellular and molecular mechanisms.

Methods

Novel object recognition and Morris water maze tests were used to evaluate the memory-ameliorating effects of TSA in APP/PS1 transgenic mice. Immunofluorescence, Western blotting, Simoa assay, and transmission electron microscopy were utilized to examine the pathology-improvement effects of TSA. Microglial activity was assessed by Western blotting and transwell migration assay. Protein-protein interactions were analyzed by co-immunoprecipitation and LC-MS/MS.

Results

TSA treatment not only reduced amyloid β (Aβ) plaques and soluble Aβ oligomers in the brain, but also effectively improved learning and memory behaviors of APP/PS1 mice. In vitro study suggested that the improvement of Aβ pathology by TSA was attributed to the enhancement of Aβ clearance, mainly by the phagocytosis of microglia, and the endocytosis and transport of microvascular endothelial cells. Notably, a meaningful discovery in the study was that TSA dramatically upregulated the expression level of albumin in cell culture, by which TSA inhibited Aβ aggregation and promoted the phagocytosis of Aβ oligomers.

Conclusions

These findings provide a new insight into the pathogenesis of AD and suggest TSA as a novel promising candidate for the AD treatment.

This study was performed using the Quanterix HD-1 Analyzer.