Synaptic gene expression changes in frontotemporal dementia due to the MAPT 10 + 16 mutation.

Aims: Mutations in the MAPT gene encoding tau protein can cause autosomal dominant neurodegenerative tauopathies including frontotemporal dementia (often with Parkinsonism). In Alzheimer's disease, the most common tauopathy, synapse loss is the strongest pathological correlate of cognitive decline. Recently, Positron Emission Tomography (PET) imaging with synaptic tracers revealed clinically relevant loss of synapses in primary tauopathies; however, the molecular mechanisms leading to synapse degeneration in primary tauopathies remain largely unknown.

Synaptic gene expression changes in frontotemporal dementia due to the 10+16 mutation.

Mutations in the gene encoding tau protein can cause autosomal dominant neurodegenerative tauopathies including frontotemporal dementia (often with Parkinsonism). In Alzheimer's disease, the most common tauopathy, synapse loss is the strongest pathological correlate of cognitive decline. Recently, PET imaging with synaptic tracers revealed clinically relevant loss of synapses in primary tauopathies; however, the molecular mechanisms leading to synapse degeneration in primary tauopathies remain largely unknown.

Transmembrane protein 97 is a potential synaptic amyloid beta receptor in human Alzheimer's disease.

Synapse loss correlates with cognitive decline in Alzheimer's disease, and soluble oligomeric amyloid beta (Aβ) is implicated in synaptic dysfunction and loss. An important knowledge gap is the lack of understanding of how Aβ leads to synapse degeneration. In particular, there has been difficulty in determining whether there is a synaptic receptor that binds Aβ and mediates toxicity.

p-tau Ser356 is associated with Alzheimer's disease pathology and is lowered in brain slice cultures using the NUAK inhibitor WZ4003.

Tau hyperphosphorylation and aggregation is a common feature of many dementia-causing neurodegenerative diseases. Tau can be phosphorylated at up to 85 different sites, and there is increasing interest in whether tau phosphorylation at specific epitopes, by specific kinases, plays an important role in disease progression. The AMP-activated protein kinase (AMPK)-related enzyme NUAK1 has been identified as a potential mediator of tau pathology, whereby NUAK1-mediated phosphorylation of tau at Ser356 prevents the degradation of tau by the proteasome, further exacerbating tau hyperphosphorylation and accumulation.

Clinical course in corticobasal syndrome and corticobasal degeneration: implications for diagnosis and management.

This scientific commentary relates to 'Clinical course of pathologically confirmed corticobasal degeneration and corticobasal syndrome', by Aiba . (https://doi.org/10.

Synaptic oligomeric tau in Alzheimer's disease - A potential culprit in the spread of tau pathology through the brain.

In Alzheimer's disease, fibrillar tau pathology accumulates and spreads through the brain and synapses are lost. Evidence from mouse models indicates that tau spreads trans-synaptically from pre- to postsynapses and that oligomeric tau is synaptotoxic, but data on synaptic tau in human brain are scarce. Here we used sub-diffraction-limit microscopy to study synaptic tau accumulation in postmortem temporal and occipital cortices of human Alzheimer's and control donors.

Predictive blood biomarkers and brain changes associated with age-related cognitive decline.

Growing evidence supports the use of plasma levels of tau phosphorylated at threonine 181, amyloid-β, neurofilament light and glial fibrillary acidic protein as promising biomarkers for Alzheimer's disease. While these blood biomarkers are promising for distinguishing people with Alzheimer's disease from healthy controls, their predictive validity for age-related cognitive decline without dementia remains unclear. Further, while tau phosphorylated at threonine 181 is a promising biomarker, the distribution of this phospho-epitope of tau in the brain is unknown.

Synaptic degeneration in Alzheimer disease.

Alzheimer disease (AD) is characterized by progressive cognitive decline in older individuals accompanied by the presence of two pathological protein aggregates - amyloid-β and phosphorylated tau - in the brain. The disease results in brain atrophy caused by neuronal loss and synapse degeneration. Synaptic loss strongly correlates with cognitive decline in both humans and animal models of AD.

Integrated methylome and phenome study of the circulating proteome reveals markers pertinent to brain health.

Characterising associations between the methylome, proteome and phenome may provide insight into biological pathways governing brain health. Here, we report an integrated DNA methylation and phenotypic study of the circulating proteome in relation to brain health. Methylome-wide association studies of 4058 plasma proteins are performed (N = 774), identifying 2928 CpG-protein associations after adjustment for multiple testing.

Characterizing the molecular and immune landscape of canine bladder cancer.

Transitional cell carcinoma (TCC), also known as urothelial carcinoma, is the most common bladder cancer in humans and dogs. Approximately one-quarter of human TCCs are muscle-invasive and associated with a high risk of death from metastasis. Canine TCC (cTCC) tumours are typically high-grade and muscle-invasive.

Botulinum toxin type A for the treatment of muscle contractures secondary to acute spinal cord injury in a young cat.

Case Summary: A 4-month-old male entire domestic shorthair cat presented for sudden onset of right thoracic monoparesis following a fall; within 18 h, the clinical signs progressed to non-ambulatory right hemiplegia with absent sensation in the distal right thoracic limb and left hemiparesis. MRI revealed changes consistent with a C6-C7 acute non-compressive nucleus pulposus extrusion with suspected secondary C5-C7 spinal cord haemorrhage. Rehabilitation exercises were started immediately after the diagnosis of acute spinal cord trauma.