Imagine a beautiful old library that starts to fall apart. The shelves sag, the books lose their spines, and the librarian’s desk becomes wobbly. Similarly, in Alzheimer’s disease, the brain undergoes changes: regions like the hippocampus become softer and show increased astrogliosis – a response of astrocytes to injury or disease. Recent research used high-resolution atomic force microscopy to examine how the mechanical properties of the hippocampus change in a mouse model of Alzheimer’s. The study revealed that certain regions in these mice are significantly softer compared to normal mice. What’s more, this softening coincided with heightened astrogliosis, suggesting a connection between amyloid pathology and alterations in brain tissue mechanics. These findings open up new avenues for exploring how altered mechanical properties impact the function and health of brain cells affected by Alzheimer’s disease. Additionally, researchers now wonder if disruptions in mechanotransduction signaling could make neurons more vulnerable to stress in their microenvironment. To dive deeper into this fascinating study, check out the full article!

Widespread neurodegeneration, enlargement of cerebral ventricles, and atrophy of cortical and hippocampal brain structures are classic hallmarks of Alzheimer’s disease (AD). Prominent macroscopic disturbances to the cytoarchitecture of the AD brain occur alongside changes in the mechanical properties of brain tissue, as reported in recent magnetic resonance elastography (MRE) measurements of human brain mechanics. Whilst MRE has many advantages, a significant shortcoming is its spatial resolution. Higher resolution “cellular scale” assessment of the mechanical alterations to brain regions involved in memory formation, such as the hippocampus, could provide fresh new insight into the etiology of AD. Characterization of brain tissue mechanics at the cellular length scale is the first stepping-stone to understanding how mechanosensitive neurons and glia are impacted by neurodegenerative disease-associated changes in their microenvironment. To provide insight into the microscale mechanics of aging brain tissue, we measured spatiotemporal changes in the mechanical properties of the hippocampus using high resolution atomic force microscopy (AFM) indentation tests on acute brain slices from young and aged wild-type mice and the APPNL–G–F mouse model. Several hippocampal regions in APPNL–G–F mice are significantly softer than age-matched wild-types, notably the dentate granule cell layer and the CA1 pyramidal cell layer. Interestingly, regional softening coincides with an increase in astrocyte reactivity, suggesting that amyloid pathology-mediated alterations to the mechanical properties of brain tissue may impact the function of mechanosensitive astrocytes. Our data also raise questions as to whether aberrant mechanotransduction signaling could impact the susceptibility of neurons to cellular stressors in their microenvironment.

Read Full Article (External Site)