Multi-omic analysis of Huntington's disease reveals a compensatory astrocyte state.

The mechanisms underlying the selective regional vulnerability to neurodegeneration in Huntington's disease (HD) have not been fully defined. To explore the role of astrocytes in this phenomenon, we used single-nucleus and bulk RNAseq, lipidomics, HTT gene CAG repeat-length measurements, and multiplexed immunofluorescence on HD and control post-mortem brains. We identified genes that correlated with CAG repeat length, which were enriched in astrocyte genes, and lipidomic signatures that implicated poly-unsaturated fatty acids in sensitizing neurons to cell death.

Xenografted human iPSC-derived neurons with the familial Alzheimer's disease APP mutation reveal dysregulated transcriptome signatures linked to synaptic function and implicate LINGO2 as a disease signaling mediator.

Alzheimer's disease (AD) is the most common cause of dementia, and disease mechanisms are still not fully understood. Here, we explored pathological changes in human induced pluripotent stem cell (iPSC)-derived neurons carrying the familial AD APP mutation after cell injection into the mouse forebrain. APP mutant iPSCs and isogenic controls were differentiated into neurons revealing enhanced Aβ production, elevated phospho-tau, and impaired neurite outgrowth in APP neurons.

Osteopontin drives neuroinflammation and cell loss in MAPT-N279K frontotemporal dementia patient neurons.

Frontotemporal dementia (FTD) is an incurable group of early-onset dementias that can be caused by the deposition of hyperphosphorylated tau in patient brains. However, the mechanisms leading to neurodegeneration remain largely unknown. Here, we combined single-cell analyses of FTD patient brains with a stem cell culture and transplantation model of FTD.

The link between SARS-CoV-2 related microglial reactivity and astrocyte pathology in the inferior olivary nucleus.

The pathological involvement of the central nervous system in SARS-CoV2 (COVID-19) patients is established. The burden of pathology is most pronounced in the brain stem including the medulla oblongata. Hypoxic/ischemic damage is the most frequent neuropathologic abnormality.

Influence of wheelchair footrest height on ischial tuberosity pressure in individuals with paraplegia.

Objective: To describe the effect of wheelchair footrest height on sitting pressures in persons with paraplegia.

Methods: Seventeen manual wheelchair users with paraplegia underwent a seat pressure examination while footrests were elevated from the initial position with the thighs parallel to the seat (p0), by 10% (position p10) and by 20% of the fibula length (position p20). We analyzed average pressure (AP), the contact surface of the body with the seat (CS), pressures on the ischial tuberosities-left (LIP) and right (RIP)--and average pressure on both ischial tuberosities (AIP).