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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 of early-stage AD pathology. Our mechanism creates pure and mixed protein dimers, followed by tissue surface adsorption, and long-term tissue agitation ultimately inducing chemical reactions forming more stable, toxic oligomer seeds that initiate AD. It is proposed that different flow stress energies and flow types in different basal brain regions produce different neurotoxic aggregates. Proliferating artery hardening is responsible for enhanced heart systolic pulses that drive energetic CSF pulses, whose critical maximum systolic pulse energy location migrates further from the heart with increasing vascular disease. Two glymphatic systems, carotid and basilar, are suggested to contain the earliest Aβ and tau AD disease pathologies. A key to the proposed AD mechanism is a comparison of early chronic traumatic encephalopathy and AD pathologies. Experiments that test the proposed mechanism are needed.

Running is a popular form of exercise that is easily accessible to various populations; endurance running, defined as distances beyond 5 km, continues to grow within the sport. Endurance running-related injuries are common in the lower extremities and are primarily overuse related. A multitude of risk factors for injury exist, including extrinsic factors, such as running distance and frequency, and intrinsic factors, such as biomechanics and nutrition status. Training and rehabilitation techniques vary with a general focus on strengthening and gradual increase in activity, but evidence is mixed, and it is difficult to generalize programs across different running populations. Management of specific running groups, including youth runners, is an area in which additional research is needed. New treatments, such as orthobiologics and wearable technology, have promising potential to optimize performance and recovery and minimize injury. However, they need to be further evaluated with high-quality studies.

Running is a popular form of exercise that is easily accessible to various populations; endurance running, defined as distances beyond 5 km, continues to grow within the sport. Endurance running-related injuries are common in the lower extremities and are primarily overuse related. A multitude of risk factors for injury exist, including extrinsic factors, such as running distance and frequency, and intrinsic factors, such as biomechanics and nutrition status. Training and rehabilitation techniques vary with a general focus on strengthening and gradual increase in activity, but evidence is mixed, and it is difficult to generalize programs across different running populations. Management of specific running groups, including youth runners, is an area in which additional research is needed. New treatments, such as orthobiologics and wearable technology, have promising potential to optimize performance and recovery and minimize injury. However, they need to be further evaluated with high-quality studies.

Cerebrospinal fluid (CSF) flowing through periarterial spaces is integral to the brain’s mechanism for clearing metabolic waste products. Experiments that track tracer particles injected into the cisterna magna (CM) of mouse brains have shown evidence of pulsatile CSF flow in perivascular spaces surrounding pial arteries, with a bulk flow in the same direction as blood flow. However, the driving mechanism remains elusive. Several studies have suggested that the bulk flow might be an artifact, driven by the injection itself. Here, we address this hypothesis with new in vivo experiments where tracer particles are injected into the CM using a dual-syringe system, with simultaneous injection and withdrawal of equal amounts of fluid. This method produces no net increase in CSF volume and no significant increase in intracranial pressure. Yet, particle-tracking reveals flows that are consistent in all respects with the flows observed in earlier experiments with single-syringe injection.

The flow of cerebrospinal fluid (CSF) through perivascular spaces surrounding the vasculature is thought to be an important part of the brain9s mechanism for clearing metabolic waste products, including those associated with disorders such as Alzheimer9s disease. Experiments that track tracer particles injected into the cisterna magna of mouse brains have shown evidence of pulsatile CSF flow in perivascular spaces around pial (surface) arteries, with a bulk (average) flow in the same direction as the blood flow. Although measurements are consistent with the idea that this flow is driven primarily by arterial pulsations, the driving mechanism is still not completely understood, and several published articles have suggested that the bulk flow might be an artifact, driven by the injection itself. Here we address this hypothesis with new in vivo experiments in which the injection of suspended tracer particles into the cisterna magna is done with a dual-syringe system, with simultaneous injection and withdrawal of equal amounts of fluid. This method produces no net increase in CSF volume and no significant increase in intracranial pressure, and yet particle-tracking reveals flows in the pial periarterial spaces that are completely consistent with the flows observed in earlier experiments with single-syringe injection.

The ring-sheared drop is a module for the International Space Station to study sheared fluid interfaces and their influence on amyloid fibril formation. A 2.54-cm diameter drop is constrained by a stationary sharp-edged ring at some latitude and sheared by the rotation of another ring in the other hemisphere. Shearing motion is conveyed primarily by the action of surface shear viscosity. Here, we simulate microgravity in the laboratory using a density-matched liquid surrounding the drop. Upon shearing, the drop’s deformation away from spherical is found to be a result of viscous and inertial forces balanced against the capillary force. We also present evidence that the deformation increases with increasing surface shear viscosity.

Predicting the non-Newtonian shear response of soft interfaces in biophysical systems and engineered products has been compromised by the use of linear (Newtonian) constitutive equations. We present a generalized constitutive equation, with tractable material properties, governing the response of Newtonian and non-Newtonian interfaces subjected to a wide range of steady shear. With experiments spanning six decades of shear rate, we capture and unify divergent reports of shear-thinning behavior of monomolecular films of the lipid dipalmitoylphosphatidylcholine, the primary constituent of mammalian cell walls and lung surfactant, at near-physiological packing densities.