The p75NTR extracellular domain: a potential molecule regulating the solubility and removal of amyloid-β

Senile plaques composed of amyloid-beta (Aβ) in the brain are one of the hallmarks of Alzheimer disease (AD). Removal of Aβ from the brain is the most important therapeutic strategy for AD. The solubility of Aβ is critical for its endocytosis, transcytosis and removal from the brain. Our recent study has found that the extracellular domain of p75NTR, the neurotrophin receptor, plays an important role in the solubility of Aβ and might be one of the endogenous mechanisms in the regulation of Aβ plaque formation. The physiologically shedded extracellular domain of p75NTR is able to inhibit Aβ aggregation and diasggregate preformed Aβ fibrils, while the full p75NTR expressed on neurites, endothelial cells and smooth muscle cells in blood-brain barrier (BBB) might initiate Aβ endocytosis and degradation, and/or remove Aβ from the brain via BBB. Understanding the roles of p75NTR in the solubility and clearance of Aβ may allow targetting p75NTR as a unique opportunity to develop therapeutic drugs for the prevention and treatment of AD.