Method for measurement of the blood–brain barrier permeability in the perfused mouse brain: application to amyloid-β peptide in wild type and Alzheimer’s Tg2576 mice

IgG-Assisted Age-Dependent Clearance of Alzheimer's Amyloid β Peptide by the Blood–Brain Barrier Neonatal Fc Receptor

“…In contrast, a significant transport of free, circulating A␤ was by Ͼ80% inhibited by the blockade of RAGE at the BBB (Fig. 1 E), as reported previously (Deane et al, 2003;LaRue et al, 2004). These findings suggest that 4G8 effectively reduces RAGE-mediated increase in circulating A␤ influx across the BBB in APPsw ϩ/Ϫ mice by sequestering circulating A␤ in plasma.…”

A multimodal RAGE-specific inhibitor reduces amyloid β–mediated brain disorder in a mouse model of Alzheimer disease

“…In order to determine whether our designated influxsensitive FPS2 blocker and the multimodal FPS-ZM1 can inhibit RAGE-mediated Aβ transport across the BBB in APP sw/0 mice in vivo, we used an arterial vascular brain perfusion technique to quantify influx of circulating Aβ into the brain, as reported (10,43). First, we reproduced earlier findings (10,43) demonstrating that Aβ40 transport across the BBB of AD mice is RAGE mediated. We showed that a RAGE-specific antibody that does not cross the BBB blocks Aβ40 transport across the BBB by inhibiting RAGE at the luminal side of brain endothelium in contrast with nonimmune (NI) IgG ( Figure 3A).…”

“…To test whether FPS-ZM1 can inhibit influx into the brain across the BBB of Aβ42, we performed an experiment as in Figure 3A infusing Aβ42 into the brain circulation of APP sw/0 mice using brain perfusion technique (43). These data showed that FSP-ZM1 blocks influx of Aβ42 into the brain to a level roughly equivalent to FPS-ZM1 inhibition of Aβ40 influx (Supplemental Figure 6), consistent with the observations that RAGE mediates influx of both Aβ40 and Aβ42 into the brain (10).…”

Alzheimer’s disease and gut microbiota

“…In AD patients, the increased blood-to-brain influx and decreased brain-to-blood efflux of A crossing the BBB lead to the A accumulation in brain. This also suggested the changed permeability of BBB and decreased A clearance of brain in AD patients LaRue et al, 2004). LPS may play a role in A accumulation and AD progression.…”