Clearance of amyloid- by circulating lipoprotein receptors (Nat Med, 2007, 13:1029-1031)

報告日期: 2007/11/20
報告時間: 16:10/17:00
報告學生: 張耀宗
講評老師: 郭余民

Clearance of amyloid-b by circulating lipoprotein receptors


Nature Medicine 13, 1029 - 1031 (2007)



Commentator: 郭余民 教授

Date:11/20/2007 pm4:10-5:00



    Amyloid b-peptide (Ab), the peptide prominent in the brain plaques with the characteristic of Alzheimer's disease (AD), was first identified from the meningeal blood vessels of the patients of AD and Downs syndrome. It is hypothesized that the accumulation of Ab in the brain is the main effect of driving AD pathogenesis. Many studies have demonstrated that soluble oligomers of Ab, but not monomers or insoluble amyloid fibrils, may be responsible for synaptic dysfunction in the brains of AD patients and in AD animal models. Because the amyloid b peptides are one of the pathological factors of Alzheimer's disease, the clearance of Ab is considered a primary therapeutic target. The transport of Ab across the Blood-Brain Barrier is involved in two main receptors, the low density lipoprotein receptor related protein 1 (LRP1) and the receptor for advanced glycation end products (RAGE). Sagare et al. reported for the first time that recombinant soluble LRP cluster IV (sLRP-IV) share the ability of systemically administered Ab-binding with lowering cerebral Ab levels and increasing peripheral Ab in plasma. This study provides proof-of-concept of the therapeutic potential of sLRP-IV for the prevention and the treatment of AD. The authors showed that sLRP-IV has the potential as a systemic Ab-lowering peptide to enhance cerebral blow flow, efflux of Ab from brain to blood, and to prevent the re-uptake of Ab from blood to brain. The results of their APP tg mouse studies also demostrated that the treatment using LRP-IV can diminish Ab deposition in brain, thereby preventing the deficits of learning and memory.


1. R.E. Tanzi, R.D. Moir and S.L. Wagner, Clearance of Alzheimer's A beta peptide: the many roads to perdition, Neuron 43 (2004) (5), pp. 605–608.

2. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 2002; 297: 353-6