Receptor for Advanced Glycation End Products: Its Role in Alzheimer's Disease and Other Neurological Diseases

Lih-Fen Lue; Douglas Gordon Walker; Sandra Jacobson; Marwan Sabbagh


Future Neurology. 2009;4(2):167-177. 

In This Article

Potential Effects of Using Soluble RAGE Mimetics as a Therapeutic Approach to Modify AD

Recent studies have found that RAGE levels decreased with the progression of cognitive decline in AD subjects, indicating that restoring circulating sRAGE to normal levels could be useful for slowing down disease progression. The potential beneficial effects of addition of bioactive forms of sRAGE mimetics in blood are illustrated in Figure 2. First, peripheral levels of RAGE ligands, such as S100/calgranulins, AGEs and HMGB1, can be reduced, which can ultimately attenuate vascular inflammation and increase integrity of the BBB. Second, by increasing circulating sRAGE levels, more Aβ peptide can be scavenged from the peripheral Aβ pool. This can prevent Aβ trafficking across the BBB to the brain. Third, since Aβ from the peripheral pool is reduced, more Aβ can be drawn out of the brain. This may eventually reduce brain amyloid load, inflammatory responses and adverse consequences due to the activation of flRAGE.

Figure 2.

Potential strategy to prevent RAGE activation in Alzheimer's disease blood-brain barrier. This figure suggests that adding (1) RAGE inhibitors or (2) sRAGE mimetics into the circulation will (3) reduce flRAGE activation by endothelial cells at the blood-brain barrier and (4) promote Aβ transport from brain to the periphery by LRP-1. This will reduce the effects of other RAGE inflammatory ligands (S100/calgranulins and AGEs) in the brain and circulation (5). Aβ = Amyloid β; AGE = Advanced glycation end product; HMGB1 = High-mobility group box 1; LRP = Low-density lipoprotein-related protein; sRAGE = Soluble receptor for advanced glycation end product.


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