We found that this endocytic receptor conferred protection against amyloid beta-protein toxicity in the presence of activated alpha(2)-macroglobulin and its down-regulation via inhibition by receptor-associated protein or transfection of cells with presenilin 1, increased susceptibility to amyloid beta-protein toxicity.
Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: a population-based autopsy study.
This colloidal formulation of QU-encapsulated LS grafted with RMP-7 and Lf (RMP-7-Lf-QU-LS) was used to traverse human brain microvascular endothelial cells (HBMECs) regulated by human astrocytes (HAs) and to treat SK-N-MC cells after an insult with cytotoxic β-amyloid (Aβ) fibrils.
High Aβ deposition was associated significantly with a lower Mini-Mental State Examination score (<27 points, p = 0.04), high systolic blood pressure (p = 0.04), carrying the apolipoprotein E epsilon 4 allele (p < 0.01), and lower plasma ApoE levels (p = 0.02), and variation in the ABCA7 (p = 0.02) and EPHA1 genes (p = 0.02).
We investigated the association of Alzheimer's disease (AD)-related rare variants APP A673T and ABCA7rs200538373-C with the levels of β-amyloid (Aβ) and parameters of metabolic and cardiovascular health in a population-based cohort of healthy middle-aged and elderly men.
In consistence with human genetic studies, increasing evidence has demonstrated that ABCA7 deficiency exacerbates Aβ pathology using in vitro and in vivo models.
Furthermore, these plant metabolites improved the lysosomal autophagy process by increasing the expression levels of Beclin-1, LC3II and cathepsin B genes for clearance of Aβ and NFT, and increased the expression of transporter proteins, P-glycoprotein (P-gp) and low density lipoprotein receptor-related protein-1 (LRP-1) for the clearance of Aβ load from brain across the blood-brain barrier (BBB) as well as increased the expression of PPAR-γ and ApoE proteins for clearance of Aβ in ApoE mediated pathway from brain.
Restoration of Pgp at the BBB enhances the elimination of the Aβ from brain alongside and inhibits the apical to basolateral movement of Aβ from the circulatory blood.
P-glycoprotein (P-gp, ABCB1) is an efflux transporter at the blood-brain barrier (BBB), which mediates clearance of beta-amyloid (Aβ) from brain into blood.
This suggests therefore that LiCl is unlikely to affect the BBB efflux of Aβ or other P-gp substrates at pharmacologically-relevant concentrations, suggesting that the Aβ-lowering effects of LiCl are unrelated to elevated BBB P-gp expression.
In this study, we investigated a possible association between 2 common ABCB1 polymorphisms, G2677T/A (Ala893Ser/Thr) and C3435T, AD, and cerebrospinal fluid (CSF) levels of Aβ.
Here, we have shown that NCAM1 peptide constructs carrying polycationic sequences derived from Aβ peptide (KKLVFF) and PrP protein (KKRPKP) significantly promote the S100A9 amyloid self-assembly in a concentration-dependent manner by making transient interactions with individual S100A9 molecules, perturbing its native structure and acting as catalysts.
ABCC6 deficiency may have increased the severity of amyloidosis by increasing the deposition in target tissues of heparan sulphate, which colocalizes spatially and temporally with amyloid proteins, and/or by decreasing the therapeutic activity of colchicine.
The highest degree of difference between the two groups was shown by the ATP-binding cassette G1 (Abcg1) which plays a crucial role in cholesterol metabolism and suppresses Aβ accumulation.
By screening a peptoid library using surface plasmon resonance imaging, amyloid inhibitory peptoid 1 (AIP1) that has high affinity to Aβ42 is identified.