Karina McDade
YOU?
Author Swipe
View article: Systemic infections alter cortical transcriptionalsignatures in Alzheimer’s disease
Systemic infections alter cortical transcriptionalsignatures in Alzheimer’s disease Open
Alzheimer’s disease (AD) is characterized by neuroinflammation, yet the impact of concurrent systemic infections on the AD brain remains poorly understood. We investigated the molecular mechanisms underlying the central nervous system resp…
View article: Decades-long elevation of interferon-α drives a Sjögren disease endotype: an interdisciplinary study
Decades-long elevation of interferon-α drives a Sjögren disease endotype: an interdisciplinary study Open
SUMMARY BACKGROUND Mechanistic heterogeneity is a major obstacle to the development of effective treatment for Sjögren disease (SjD) and there is a pressing need to stratify SjD according to precision medicine principles. Aberrant activati…
View article: Distinct Cellular Phenotypes of Language and Executive Decline in Amyotrophic Lateral Sclerosis
Distinct Cellular Phenotypes of Language and Executive Decline in Amyotrophic Lateral Sclerosis Open
Cognitive manifestations, including impairment in language and executive functions, are seen in amyotrophic lateral sclerosis (ALS), but the mechanisms that underlie these deficits remain unclear. To address this, we mapped prefrontal cort…
View article: Cell state-dependent allelic effects and contextual Mendelian randomization analysis for human brain phenotypes
Cell state-dependent allelic effects and contextual Mendelian randomization analysis for human brain phenotypes Open
Gene expression quantitative trait loci are widely used to infer relationships between genes and central nervous system (CNS) phenotypes; however, the effect of brain disease on these inferences is unclear. Using 2,348,438 single-nuclei pr…
View article: Kisspeptin is elevated in the brain after intracerebral haemorrhagic stroke
Kisspeptin is elevated in the brain after intracerebral haemorrhagic stroke Open
Intracerebral haemorrhage (ICH) is the most severe subtype of stroke, with a 2-year mortality of nearly 50% and the greatest rate of disability amongst stroke survivors. Whilst treatment options for ICH remain limited, the condition requir…
View article: Cell-autonomous immune dysfunction driven by disrupted autophagy in <i>C9orf72</i> -ALS iPSC-derived microglia contributes to neurodegeneration
Cell-autonomous immune dysfunction driven by disrupted autophagy in <i>C9orf72</i> -ALS iPSC-derived microglia contributes to neurodegeneration Open
Although microglial activation is widely found in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), the underlying mechanism(s) are poorly understood. Here, using human-induced pluripotent stem cell–derived microglia-l…
View article: Single-cell Mendelian randomisation identifies cell-type specific genetic effects on human brain disease and behaviour
Single-cell Mendelian randomisation identifies cell-type specific genetic effects on human brain disease and behaviour Open
Translating genome-wide association loci to therapies requires knowledge of the causal genes, their directionality of effect and the cell-types in which they act. To infer these relationships in the human brain, we implemented Mendelian ra…
View article: Random forest modelling demonstrates microglial and protein misfolding features to be key phenotypic markers in <scp> <i>C9orf72</i> ‐ALS </scp>
Random forest modelling demonstrates microglial and protein misfolding features to be key phenotypic markers in <span> <i>C9orf72</i> ‐ALS </span> Open
Clinical heterogeneity observed across patients with amyotrophic lateral sclerosis (ALS) is a known complicating factor in identifying potential therapeutics, even within cohorts with the same mutation, such as C9orf72 hexanucleotide repea…
View article: Mitochondrial bioenergetic dysfunction and cryptic splicing of stathmin-2 are neuropathological markers of disease duration in sporadic amyotrophic lateral sclerosis
Mitochondrial bioenergetic dysfunction and cryptic splicing of stathmin-2 are neuropathological markers of disease duration in sporadic amyotrophic lateral sclerosis Open
A striking feature of sporadic amyotrophic lateral sclerosis (ALS) is the marked heterogeneity in disease duration; despite the stark median survival of three years from symptom onset, 10-20% of people with ALS survive longer than 10 years…
View article: Nrf2 activation in the human brain after stroke due to supratentorial intracerebral haemorrhage: a case–control study
Nrf2 activation in the human brain after stroke due to supratentorial intracerebral haemorrhage: a case–control study Open
Aims Pharmacological activation of the antioxidative transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) improves outcomes in experimental models of intracerebral haemorrhage (ICH). However, the Nrf2 pathway has not bee…
View article: Reactive astrocytes acquire neuroprotective as well as deleterious signatures in response to Tau and Aß pathology
Reactive astrocytes acquire neuroprotective as well as deleterious signatures in response to Tau and Aß pathology Open
View article: Random forest modelling of neuropathological features identifies microglial activation as an accurate pathological classifier of C9orf72-related amyotrophic lateral sclerosis
Random forest modelling of neuropathological features identifies microglial activation as an accurate pathological classifier of C9orf72-related amyotrophic lateral sclerosis Open
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are regarded as two ends of a pathogenetic spectrum, termed ALS-frontotemporal spectrum disorder (ALS-FTSD). However, it is currently difficult to predict where on the s…
View article: <scp>NLRP3</scp> inflammasome as a key molecular target underlying cognitive resilience in amyotrophic lateral sclerosis
<span>NLRP3</span> inflammasome as a key molecular target underlying cognitive resilience in amyotrophic lateral sclerosis Open
Up to 50% of amyotrophic lateral sclerosis patients present with cognitive deficits in addition to motor dysfunction, but the molecular mechanisms underlying diverse clinical and pathological presentations remain poorly understood. There i…
View article: Dysregulation in Subcellular Localization of Myelin Basic Protein mRNA Does Not Result in Altered Myelination in Amyotrophic Lateral Sclerosis
Dysregulation in Subcellular Localization of Myelin Basic Protein mRNA Does Not Result in Altered Myelination in Amyotrophic Lateral Sclerosis Open
Pathological hallmarks of amyotrophic lateral sclerosis (ALS), including protein misfolding, are well established in oligodendrocytes. More recently, an RNA trafficking deficit of key myelin proteins has been suggested in oligodendrocytes …
View article: Mitochondrial bioenergetic deficits in C9orf72 amyotrophic lateral sclerosis motor neurons cause dysfunctional axonal homeostasis
Mitochondrial bioenergetic deficits in C9orf72 amyotrophic lateral sclerosis motor neurons cause dysfunctional axonal homeostasis Open
View article: Spatial transcriptomics identifies spatially dysregulated expression of <i>GRM3</i> and <i>USP47</i> in amyotrophic lateral sclerosis
Spatial transcriptomics identifies spatially dysregulated expression of <i>GRM3</i> and <i>USP47</i> in amyotrophic lateral sclerosis Open
Aims The mechanisms underlying the selective degeneration of motor neurones in amyotrophic lateral sclerosis (ALS) are poorly understood. The aim of this study was to implement spatially resolved RNA sequencing in human post mortem cortica…
View article: Improved detection of RNA foci in C9orf72 amyotrophic lateral sclerosis post-mortem tissue using BaseScope™ shows a lack of association with cognitive dysfunction
Improved detection of RNA foci in C9orf72 amyotrophic lateral sclerosis post-mortem tissue using BaseScope™ shows a lack of association with cognitive dysfunction Open
The C9orf72 hexanucleotide repeat expansion is the commonest known genetic mutation in amyotrophic lateral sclerosis. A neuropathological hallmark is the intracellular accumulation of RNA foci. The role that RNA foci play in the pathogenes…
View article: Dysregulation of AMPA receptor subunit expression in sporadic ALS post‐mortem brain
Dysregulation of AMPA receptor subunit expression in sporadic ALS post‐mortem brain Open
Amyotrophic lateral sclerosis (ALS) is characterised by progressive motor neuron degeneration. Although there are over 40 genes associated with causal monogenetic mutations, the majority of ALS patients are not genetically determined. Caus…
View article: Executive, language and fluency dysfunction are markers of localised TDP-43 cerebral pathology in non-demented ALS
Executive, language and fluency dysfunction are markers of localised TDP-43 cerebral pathology in non-demented ALS Open
Objective Approximately 35% of patients with amyotrophic lateral sclerosis (ALS) exhibit mild cognitive deficits in executive functions, language and fluency, without dementia. The precise pathology of these extramotor symptoms has remaine…
View article: Neuronal clusterin expression is associated with cognitive protection in amyotrophic lateral sclerosis
Neuronal clusterin expression is associated with cognitive protection in amyotrophic lateral sclerosis Open
Aims Clusterin is a topologically dynamic chaperone protein with the ability to participate in both intra‐ and extacellular proteostasis. Clusterin has been shown to be upregulated in the spinal cord of patients with amyotrophic lateral sc…
View article: Clusterin protects neurons against intracellular proteotoxicity
Clusterin protects neurons against intracellular proteotoxicity Open
It is now widely accepted in the field that the normally secreted chaperone clusterin is redirected to the cytosol during endoplasmic reticulum (ER) stress, although the physiological function(s) of this physical relocation remain unknown.…
View article: Effect of broodstock holding environment on egg quality in farmed brown trout (Salmo trutta)
Effect of broodstock holding environment on egg quality in farmed brown trout (Salmo trutta) Open
Brown trout (Salmo trutta) broodstock from a single population were separated prior to spawning and exposed to two different holding environments: a ‘raceway system’ and a ‘tank system’. Eggs were stripped from females and 13 measures of e…