  The mechanisms behind waste clearance from deep within the parenchyma of the
brain remain unclear to this date. Experimental evidence has shown that one
pathway for waste clearance, termed intramural periarterial drainage (IPAD), is
the rapid drainage of interstitial fluid (ISF) via basement membranes (BM) of
the smooth muscle cells (SMC) of cerebral arteries and its failure is closely
associated with the pathology of Alzheimer's disease (AD). We have previously
shown that arterial pulsations from the heart beat are not strong enough to
drive waste clearance. Here we demonstrate computational evidence for a
mechanism for cerebral waste clearance that is driven by functional hyperaemia,
that is, the dilation of cerebral arteries as a consequence of increased
neuronal demand. This mechanism is based on our model for fluid flow through
the vascular basement membrane. It accounts for waste clearance rates observed
in mouse experiments and aligns with pathological observations as well as
recommendations to lower the individual risk of AD, such as keeping mentally
and physically active.
