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Shear-Induced Amyloid Aggregation in the Brain: V. Are Alzheimer’s and Other Amyloid Diseases Initiated in the Lower Brain and Brainstem by Cerebrospinal Fluid Flow Stresses?
- Source :
- Journal of Alzheimer's Disease
- Publication Year :
- 2021
- Publisher :
- IOS Press, 2021.
-
Abstract
- Amyloid-β (Aβ) and tau oligomers have been identified as neurotoxic agents responsible for causing Alzheimer’s disease (AD). Clinical trials using Aβ and tau as targets have failed, giving rise to calls for new research approaches to combat AD. This paper provides such an approach. Most basic AD research has involved quiescent Aβ and tau solutions. However, studies involving laminar and extensional flow of proteins have demonstrated that mechanical agitation of proteins induces or accelerates protein aggregation. Recent MRI brain studies have revealed high energy, chaotic motion of cerebrospinal fluid (CSF) in lower brain and brainstem regions. These and studies showing CSF flow within the brain have shown that there are two energetic hot spots. These are within the third and fourth brain ventricles and in the neighborhood of the circle of Willis blood vessel region. These two regions are also the same locations as those of the earliest Aβ and tau AD pathology. In this paper, it is proposed that cardiac systolic pulse waves that emanate from the major brain arteries in the lower brain and brainstem regions and whose pulse waves drive CSF flows within the brain are responsible for initiating AD and possibly other amyloid diseases. It is further proposed that the triggering of these diseases comes about because of the strengthening of systolic pulses due to major artery hardening that generates intense CSF extensional flow stress. Such stress provides the activation energy needed to induce conformational changes of both Aβ and tau within the lower brain and brainstem region, producing unique neurotoxic oligomer molecule conformations that induce AD.
- Subjects :
- 0301 basic medicine
heart failure
Plaque, Amyloid
tau Proteins
shear
Protein aggregation
Models, Biological
Protein Aggregation, Pathological
cerebrospinal fluid
oligomer
arteries
03 medical and health sciences
Amyloid disease
strain
0302 clinical medicine
Cerebrospinal fluid
Alzheimer Disease
Stress, Physiological
medicine.artery
medicine
Humans
Amyloid-β
tau
Brain Ventricle
Amyloid beta-Peptides
ventricles
Pulse (signal processing)
Chemistry
General Neuroscience
systolic pulse
Brain
General Medicine
Hypothesis
extensional flow
Psychiatry and Mental health
Clinical Psychology
030104 developmental biology
medicine.anatomical_structure
Disease Progression
Brainstem
atherosclerosis
Geriatrics and Gerontology
Neuroscience
fluid flow stress
030217 neurology & neurosurgery
Brain Stem
Circle of Willis
Blood vessel
Subjects
Details
- ISSN :
- 18758908 and 13872877
- Volume :
- 79
- Database :
- OpenAIRE
- Journal :
- Journal of Alzheimer's Disease
- Accession number :
- edsair.doi.dedup.....f165c4af0b528be28146931bdcbd3738