Investigation of pathogenetic mechanism, prevention and treatment of Alzheimer's disease via systemic approaches

Abstract

Alzheimer's disease (AD) becomes a major disease affecting the elderly with high prevalence. However, no disease-modifying therapies are currently available. AD has long been regarded as a disease of brain itself, but recent studies found that systemic disorders are associated with risk for AD. During the period of Twelfth Five-Year Plan for National Economic and Social Development, our team tried to reveal the pathogenesis, targets, amyloid β-protein (Aβ) clearence pathway and drugs from both central and peripheral approaches, and have discovered: 1) the ratio of p75 neurotrophin receptor (p75NTR) in the brain of AD regulates the over?production and clearence of Aβ in sporadic AD. 2) Peripheral Aβ is able to enter brain, forms AD-type pathologies and induces neuronal deficits, revealing the peripheral mechanism of AD. 3) The effectiveness and safety of brain A β clearance by peripheral organs and tissues has been verified. Based on these findings, we proposed a systemic view of AD, to understand pathogenesis and develop novel diagnostic methods and therapies from a systemic approach.

DOI: 10.3969/j.issn.1672-6731.2018.01.004