In all of the preceding, the rates of elimination by various routes have been considered almost as if they are constant. However, reduction in the overall clearance and thus in the rates of elimination by some of the routes are likely to be very important in the development of Alzheimer’s disease [422]. In this regard LRP1 expression has been found to be reduced and RAGE expression increased with age [478, 513]. Similarly perivascular elimination has been found to decrease with age possibly as a result of decreased variations in the size of arteries and arterioles during the cardiac cycle [514] (see Sect. 3.2). All of these changes will tend to increase Aβ ISF concentration and hence lead to increased formation of plaques and vascular Aβ deposits.