title: Modeling the Role of the Glymphatic Pathway and Cerebral Blood Vessel Properties in Alzheimer's Disease Pathogenesis.
abstract: Alzheimer's disease (AD) is the most common cause of dementia in the elderly, affecting over 10% population over the age of 65 years. Clinically, AD is described by the symptom set of short term memory loss and cognitive decline, changes in mentation and behavior, and eventually long-term memory deficit as the disease progresses. On imaging studies, significant atrophy with subsequent increase in ventricular volume have been observed. Pathology on post-mortem brain specimens demonstrates the classic findings of increased beta amyloid (Aβ) deposition and the presence of neurofibrillary tangles (NFTs) within affected neurons. Neuroinflammation, dysregulation of blood-brain barrier transport and clearance, deposition of Aβ in cerebral blood vessels, vascular risk factors such as atherosclerosis and diabetes, and the presence of the apolipoprotein E4 allele have all been identified as playing possible roles in AD pathogenesis. Recent research has demonstrated the importance of the glymphatic system in the clearance of Aβ from the brain via the perivascular space surrounding cerebral blood vessels. Given the variety of hypotheses that have been proposed for AD pathogenesis, an interconnected, multilayer model offers a unique opportunity to combine these ideas into a single unifying model. Results of this model demonstrate the importance of vessel stiffness and heart rate in maintaining adequate clearance of Aβ from the brain.
authors.affiliation: University of Pittsburgh Medical Center, Department of Neurology, Pittsburgh, Pennsylvania, United States of America; Institute for Systems Research, University of Maryland, College Park, Maryland, United States of America.
authors.forename: Christina Rose
authors.initials: CR
authors.lastname: Kyrtsos
authors.affiliation: Institute for Systems Research, University of Maryland, College Park, Maryland, United States of America; Department of Electrical and Computer Engineering, University of Maryland, College Park, Maryland, United States of America.
authors.forename: John S
authors.initials: JS
authors.lastname: Baras
mesh_terms: D000368:Aged; D000375:Aging; D000483:Alleles; D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000235:genetics; D001812:Blood-Brain Barrier / Q000378:metabolism; D001919:Bradycardia / Q000503:physiopathology; D001921:Brain / Q000378:metabolism; D002536:Cerebral Arteries / Q000502:physiology*; D060825:Cognitive Dysfunction / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000502:physiology; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008954:Models, Biological; D011859:Radiography
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1