Inadequate Amyloid Clearance in Alzheimer's Disease: The Possible Role of TTR Transporter Protein and LRP-1 Receptor

Alzheimer's disease affects large populations worldwide. However, there is not yet a blood-based minimally invasive biomarker that can provide a definitive diagnosis. There is also no curative treatment. Extracellular senile amyloid plaques, which are formed by the accumulation of amyloid derivatives in the central nervous system, have an important role in the development of Alzheimer's disease. The reason for the accumulation of amyloid derivatives in the central nervous system is shown as excess production by faulty proteolysis of amyloid precursor protein by enzymes. However, one of the causes of amyloid deposition in the central nervous system is insufficient clearance of these derivatives. Since amyloid production cannot be balanced with amyloid clearance in Alzheimer's disease, accumulation of monomers, oligomers, insoluble fibrils and plaques is observed in the central nervous system. It is argued that the deficiency or loss of function of the transthyretin transporter protein, which is thought to be involved in this removal, and LRP-1, a blood-brain barrier receptor, also may predispose to Alzheimer's disease. In this review, possible biomarkers for Alzheimer's disease, transthyretin and LRP-1-mediated amyloid clearance were examined.