Background:
Vascular wall amyloidosis, one of the important cell and tissue changes in dementiae of the Alzheimer type, is characterized by massive deposition of β-amyloid in the walls of leptomeningeal and cortical arteries and arterioles, as well as in vessels in the brainstem and cerebellum. This deposition depends critically on both lipoprotein isoform and cholesterol, which has prompted research on the link between coronary disease and Alzheimer's disease. High cholesterol diets were found to induce accumulation of β-amyloid in the brain. Anthocyanins from blackcurrant extract (BCE) may have beneficial effects on Alzheimer dementiae via other target points than cholesterol lowering.
Materials and Methods:
Flow-dependent isometric tension was measured in segments of isolated human intracerebral arteries from consciousness areas, coming from brain surgery. The blood vessel segments were stretched by 1.5 g pretension. The flow of the blood substitute solution (Krebs) was varied in the steps 3, 5, 20, 40, and 100 mL/min. Krebs solution without and with addition of 0.01% BCE (BC ACL-1.5, BerryPharma AG, Leichlingen, Germany) was used as superfusate. Nanotechnologic biosensor ellipsometry, photometric methods, ELISAs and EIAs were applied. VLDLapoE4/E4 (10 mg/dL) from genotypized patients and human β-amyloid peptide (1-42) (Aβ) were used in the ellipsometric measurements.
Results:
In the controls (n = 14), the smooth muscle cells of the brain arteries relaxed from 1.416 ± 0.009 g to 1.011 ± 0.033 g (p < 0.001) corresponding to 28.6% of their initial tone. Under blackcurrant liquid extract (n = 5), the decrease in wall tension was much more distinct. Vascular tone decreased from 1.454 ± 0.010 g (flow 3 mL/min) to 0.867 ± 0.052 g (flow 100 mL/min) (p < 0.001; against the control p < 0.0354). This is equivalent to a 40.4% reduction in tension, a 45.2% increase in flow-dependent relaxation, and an estimated 50.7% rise in blood perfusion under blackcurrant. BCE (0.001%) is strongly bound to membrane integral proteoheparan sulphate (HS-PG), the natural flow sensor and peripheral lipoprotein receptor, as measured by ellipsometric techniques. Addition of VLDLapoE4/E4, Aβ, and Ca
2+
ions (2.52 to 17.64 mmol/L) to HS-PG adsorbed to a silica surface led to quaternary Alzheimer plaque formation in control experiments. Preincubation of HS-PG with BCE reduced VLDL docking by 5.9%, ternary plaque formation with Aβ by 11.6%, and quaternary calcified Alzheimer nanoplaque formation by 17.3%.
Conclusion:
The flow experiments impressively show that BCE clearly improves endothelial function by an additional NO release. This vasodilatation together with the reduction of Alzheimer nanoplaque neoformation, detected here for the first time as a novel pleiotropic action of BCE, may have a beneficial effect on the cognitive functions in dementiae of the Alzheimer type, in the prevention of TIA and stroke.
Differential in vitro interactions of the Janus kinase inhibitor ruxolitinib with human SLC drug transporters
