%A Diem,Alexandra K. %A MacGregor Sharp,Matthew %A Gatherer,Maureen %A Bressloff,Neil W. %A Carare,Roxana O. %A Richardson,Giles %D 2017 %J Frontiers in Neuroscience %C %F %G English %K Alzheimer’s disease,Cerebrovascular Circulation,perivascular drainage,intramural periarterial drainage,cerebral lymphatics %Q %R 10.3389/fnins.2017.00475 %W %L %M %P %7 %8 2017-August-24 %9 Original Research %+ Alexandra K. Diem,Computational Engineering and Design, Faculty of Engineering & the Environment, University of Southampton,Southampton, United Kingdom,a.k.diem@soton.ac.uk %# %! Arterial pulsations cannot drive periarterial drainage %* %< %T Arterial Pulsations cannot Drive Intramural Periarterial Drainage: Significance for Aβ Drainage %U https://www.frontiersin.org/articles/10.3389/fnins.2017.00475 %V 11 %0 JOURNAL ARTICLE %@ 1662-453X %X Alzheimer's Disease (AD) is the most common form of dementia and to date there is no cure or efficient prophylaxis. The cognitive decline correlates with the accumulation of amyloid-β (Aβ) in the walls of capillaries and arteries. Our group has demonstrated that interstitial fluid and Aβ are eliminated from the brain along the basement membranes of capillaries and arteries, the intramural periarterial drainage (IPAD) pathway. With advancing age and arteriosclerosis, the stiffness of arterial walls, this pathway fails in its function and Aβ accumulates in the walls of arteries. In this study we tested the hypothesis that arterial pulsations drive IPAD and that a valve mechanism ensures the net drainage in a direction opposite to that of the blood flow. This hypothesis was tested using a mathematical model of the drainage mechanism. We demonstrate firstly that arterial pulsations are not strong enough to produce drainage velocities comparable to experimental observations. Secondly, we demonstrate that a valve mechanism such as directional permeability of the IPAD pathway is necessary to achieve a net reverse flow. The mathematical simulation results are confirmed by assessing the pattern of IPAD in mice using pulse modulators, showing no significant alteration of IPAD. Our results indicate that forces other than the cardiac pulsations are responsible for efficient IPAD.