Modeling the Role of the Glymphatic Pathway and Cerebral Blood Vessel Properties in Alzheimer's Disease Pathogenesis

• Published in: PloS one Vol. 10; no. 10; p. e0139574
• Main Authors: Kyrtsos, Christina Rose, Baras, John S
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08-10-2015; Public Library of Science (PLoS)
• Subjects: Aged; Aging; Alleles; Alzheimer Disease - pathology; Alzheimer's disease; Alzheimers disease; Amyloid beta-Peptides - metabolism; Apolipoprotein E4; Apolipoprotein E4 - genetics; Apolipoproteins; Arteriosclerosis; Atherosclerosis; Atrophy; Autopsy; Blood vessels; Blood-brain barrier; Blood-Brain Barrier - metabolism; Bradycardia - physiopathology; Brain - metabolism; Brain research; Care and treatment; Cerebral Arteries - physiology; Cognitive ability; Cognitive Dysfunction - pathology; Dementia disorders; Deposition; Diabetes mellitus; Elderly; Female; Geriatrics; Health aspects; Health risks; Heart rate; Hippocampus - diagnostic imaging; Hippocampus - physiology; Humans; Hypertension; Inflammation; Long term memory; Low Density Lipoprotein Receptor-Related Protein-1 - metabolism; Magnetic Resonance Imaging; Male; Models, Biological; Neurofibrillary tangles; Neuroimaging; Neurons; Older people; Pathogenesis; Peptides; Radiography; Risk analysis; Risk factors; Short term memory; Stiffness; Ventricle; β-Amyloid; United States; United States > US; Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0139574

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.