An Alzheimer's Disease Mechanism Based on Early Pathology, Anatomy, Vascular-Induced Flow, and Migration of Maximum Flow Stress Energy Location with Increasing Vascular Disease.

ABSTRACT: This paper suggests a chemical mechanism for the earliest stages of Alzheimer's disease (AD). Cerebrospinal fluid (CSF) flow stresses provide the energy needed to induce molecular conformation changes leading to AD by initiating amyloid-β (Aβ) and tau aggregation. Shear and extensional flow stresses initiate aggregation in the laboratory and in natural biophysical processes. Energy-rich CSF flow regions are mainly found in lower brain regions. MRI studies reveal flow stress "hot spots" in basal cisterns and brain ventricles that have chaotic flow properties that can distort molecules such as Aβ and tau trapped in these regions into unusual conformations. Such fluid disturbance is surrounded by tissue deformation. There is strong mapping overlap between the locations of these hot spots and

SUBMITTER: Trumbore CN 

PROVIDER: S-EPMC9661328 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature