The glymphatic system and Alzheimer’s disease: possible connection?

Abstract — Alzheimer’s disease (AD) is the most common cause of dementia in the elderly, accounting for 60-80 % of all dementias. Symptoms of AD include memory loss (initially short term, later on long term as well), changes in mood and sun-downing. Magnetic resonance imaging (MRI) shows diffuse cortical atrophy and enlargement of the lateral ventricles due to neuronal cell loss. At the cellular level, neuroinflammation, activation of microglia, deposition of beta amyloid (Aβ) in the brain parenchyma and cerebral vasculature, and increases in the permeability of the blood-brain barrier (BBB) have all been observed as well. A newly developed theory purports that the glymphatic system of the brain may play a significant role in AD pathogenesis. This paper presents an initial mathematical model of the glymphatic system and studies how changes of transporter density and deposition of Aβ at the BBB changes clearance of Aβ. Changes in local neuronal cell density were also modeled. This represents one of the first attempts to computationally study the role of the glymphatic system in AD. Keywords-Alzheimer’s disease, math model, glymphatic system, LRP1, Aβ clearance I