The protocol for an observational Australian cohort study of CADASIL: The AusCADASIL study.

Introduction: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare genetic condition with a broad phenotypic presentation. This study aims to establish the first Australian cohort of individuals affected by CADASIL (AusCADASIL) and examine its clinical features and longitudinal course, and to investigate neuroimaging and blood biomarkers to assist in early diagnosis and identify disease progression.

Methods: Participants will be recruited from six study centres across Australia for an observational study of CADASIL.

Fluid biomarkers of the neurovascular unit in cerebrovascular disease and vascular cognitive disorders: A systematic review and meta-analysis.

Background: The disruption of the neurovascular unit (NVU), which maintains the integrity of the blood brain barrier (BBB), has been identified as a critical mechanism in the development of cerebrovascular and neurodegenerative disorders. However, the understanding of the pathophysiological mechanisms linking NVU dysfunction to the disorders is incomplete, and reliable blood biomarkers to measure NVU dysfunction are yet to be established. This systematic review and meta-analysis aimed to identify biomarkers associated with BBB dysfunction in large vessel disease, small vessel disease (SVD) and vascular cognitive disorders (VCD).

Molecular biomarkers for vascular cognitive impairment and dementia.

As disease-specific interventions for dementia are being developed, the ability to identify the underlying pathology and dementia subtypes is increasingly important. Vascular cognitive impairment and dementia (VCID) is the second most common cause of dementia after Alzheimer disease, but progress in identifying molecular biomarkers for accurate diagnosis of VCID has been relatively limited. In this Review, we examine the roles of large and small vessel disease in VCID, considering the underlying pathophysiological processes that lead to vascular brain injury, including atherosclerosis, arteriolosclerosis, ischaemic injury, haemorrhage, hypoperfusion, endothelial dysfunction, blood-brain barrier breakdown, inflammation, oxidative stress, hypoxia, and neuronal and glial degeneration.

Evaluating Cellular Viability by iTRAQ Proteomic Profiling.

Cellular health, functionality, response to environment, and other variables affecting cell, tissue, or organ viability are reflected in the cellular proteomes and metabolomes. These "omic" profiles are in constant flux even during normal cellular functioning, to maintain cellular homeostasis, in response to small environmental changes and maintenance of optimal cell viability. However proteomic "fingerprints" can also provide insight into cellular ageing, response to disease, adjustment to environmental changes, and other variables that impact cellular viability.

Tau target identification reveals NSF-dependent effects on AMPA receptor trafficking and memory formation.

Microtubule-associated protein tau is a central factor in Alzheimer's disease and other tauopathies. However, the physiological functions of tau are unclear. Here, we used proximity-labelling proteomics to chart tau interactomes in primary neurons and mouse brains in vivo.

The use of isothermal titration calorimetry for the assay of enzyme activity: Application in higher education practical classes.

Determination of enzyme activity is crucial for discovery, research, and development in life sciences. The activity of enzymes is routinely determined using spectrophotometric assays that measure rates of substrate consumption or product formation. Though colorimetric-based detection systems are simple, rapid, and economical to perform, the majority of enzymes are unsuitable for this technique as their substrates/products do not absorb in the UV or visible range.

Alzheimer's disease: Ablating single master site abolishes tau hyperphosphorylation.

Hyperphosphorylation of the neuronal tau protein is a hallmark of neurodegenerative tauopathies such as Alzheimer's disease. A central unanswered question is why tau becomes progressively hyperphosphorylated. Here, we show that tau phosphorylation is governed by interdependence- a mechanistic link between initial site-specific and subsequent multi-site phosphorylation.

Assay of Fatty Acids and Their Role in the Prevention and Treatment of COVID-19.

Since the emergence of COVID-19, concerted worldwide efforts have taken place to minimize global spread of the contagion. Its widespread effects have also facilitated evolution of new strains, such as the delta and omicron variants, which emerged toward the end of 2020 and 2021, respectively. While these variants appear to be no more deadly than the previous alpha, beta, and gamma strains, and widespread population vaccinations notwithstanding, greater virulence makes the challenge of minimizing spread even greater.

Evaluating Enzymatic Productivity-The Missing Link to Enzyme Utility.

Kinetic productivity analysis is critical to the characterization of enzyme catalytic performance and capacity. However, productivity analysis has been largely overlooked in the published literature. Less than 0.

Differential mitochondrial protein interaction profile between human translocator protein and its A147T polymorphism variant.

The translocator protein (TSPO) has been implicated in mitochondrial transmembrane cholesterol transport, brain inflammation, and other mitochondrial functions. It is upregulated in glial cells during neuroinflammation in Alzheimer's disease. High affinity TSPO imaging radioligands are utilized to visualize neuroinflammation.

Extending the Depth of Human Plasma Proteome Coverage Using Simple Fractionation Techniques.

Human plasma is one of the most widely used tissues in clinical analysis, and plasma-based biomarkers are used for monitoring patient health status and/or response to medical treatment to avoid unnecessary invasive biopsy. Data-driven plasma proteomics has suffered from a lack of throughput and detection sensitivity, largely due to the complexity of the plasma proteome and in particular the enormous quantitative dynamic range, estimated to be between 9 and 13 orders of magnitude between the lowest and the highest abundance protein. A major challenge is to identify workflows that can achieve depth of plasma proteome coverage while minimizing the complexity of the sample workup and maximizing the sample throughput.

Resveratrol: A "miracle" drug in neuropsychiatry or a cognitive enhancer for mice only? A systematic review and meta-analysis.

Background: Over the last decade resveratrol has been trialled for the prevention and treatment of cognitive decline; however, the results have shown a conflict between human studies compared with animal studies, especially on cognition, blood pressure, neuroimaging, and mood.

Methods: Human clinical trials and animal studies published prior to January 2020, were identified searching across major electronic databases. PRISMA guidelines were used for data extraction, which was independently performed by two authors.

Comparative proteomics of the toxigenic diazotroph Raphidiopsis raciborskii (cyanobacteria) in response to iron.

Raphidiopsis raciborskii is an invasive bloom-forming cyanobacteria with the flexibility to utilize atmospheric and fixed nitrogen. Since nitrogen-fixation has a high requirement for iron as an ezyme cofactor, we hypothesize that iron availability would determine the success of the species under nitrogen-fixing conditions. This study compares the proteomic response of cylindrospermopsin-producing and non-toxic strains of R.

Genetic and environmental determinants of variation in the plasma lipidome of older Australian twins.

The critical role of blood lipids in a broad range of health and disease states is well recognised but less explored is the interplay of genetics and environment within the broader blood lipidome. We examined heritability of the plasma lipidome among healthy older-aged twins (75 monozygotic/55 dizygotic pairs) enrolled in the Older Australian Twins Study (OATS) and explored corresponding gene expression and DNA methylation associations. 27/209 lipids (13.

Plasma lipidomic biomarker analysis reveals distinct lipid changes in vascular dementia.

Vascular dementia (VaD) is a complex neurocognitive disorder secondary to a variety of cerebrovascular lesions. Numerous studies have shown that lipid metabolism is involved in the pathobiology of the disease. We examined the plasma lipid profiles in VaD, with the expectation of identifying reliable lipid biomarkers for VaD.

Fluid Biomarkers and APOE Status of Early Onset Alzheimer's Disease Variants: A Systematic Review and Meta-Analysis.

Background: Numerous studies have reported on cerebrospinal fluid (CSF) and blood biomarkers of Alzheimer's disease (AD); however, to date, none has compared biomarker patterns across the early-onset subtypes, i.e., early onset sporadic AD (EOsAD) and autosomal dominant AD (ADAD), qualitatively and quantitatively.

Quantitative Assays of Plasma Apolipoproteins.

The apolipoproteins are well known for their roles in both health and disease, as components of plasma lipoprotein particles, such as high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), chylomicrons, and metabolic, vascular- and inflammation-related disorders, such as cardiovascular disease, atherosclerosis, metabolic syndrome, and diabetes. Increasingly, their roles in neurovascular and neurodegenerative disorders are also being elucidated. They play major roles in lipid and cholesterol transport between blood and organs and are, therefore, critical to maintenance and homeostasis of the lipidome, with apolipoprotein-lipid interactions, including cholesterol, fatty acids, triglycerides, phospholipids, and isoprostanes.

Blood fatty acids in Alzheimer's disease and mild cognitive impairment: A meta-analysis and systematic review.

Plasma fatty acids have been reported to be dysregulated in mild cognitive impairment (MCI) and Alzheimer's disease (AD), though outcomes are not always consistent, and subject numbers often small. Our aim was to use a meta-analysis and systematic review approach to identify if plasma fatty acid dysregulation would be observed in case control studies of AD and MCI. Six databases were searched for studies reporting quantified levels of fatty acids in MCI and/or AD individuals, relative to cognitively normal controls.

Mapping p38α mitogen-activated protein kinase signaling by proximity-dependent labeling.

Mitogen-activated protein (MAP) kinase signaling is central to multiple cellular responses and processes. MAP kinase p38α is the best characterized member of the p38 MAP kinase family. Upstream factors and downstream targets of p38α have been identified in the past by conventional methods such as coimmunoprecipitation.

Nanoparticles as contrast agents for the diagnosis of Alzheimer's disease: a systematic review.

Nanoparticle (NP)-based magnetic contrast agents have opened the potential for MRI to be used for early diagnosis of Alzheimer's disease (AD). This article aims to review the current progress of research in this field. A comprehensive literature search was performed based on PubMed, Medline, EMBASE, PsychINFO and Scopus databases using the following terms: 'Alzheimer's disease' AND 'nanoparticles' AND 'Magnetic Resonance Imaging.

APOE Genotype Differentially Modulates Plasma Lipids in Healthy Older Individuals, with Relevance to Brain Health.

Apolipoprotein E (APOE) genotype is an established genetic risk factor for sporadic Alzheimer's disease (AD) but the extent to which APOE genotype influences the plasma lipidome is unknown, even though lipids are potential diagnostic or prognostic biomarkers for AD. We quantified plasma lipids using untargeted liquid chromatography coupled mass spectrometry in a total of 152 non-demented participants aged 65-100 years carrying at least one ɛ2 or ɛ4 allele (ɛ2/ɛ2 or ɛ2/ɛ3, n = 38: ɛ4/ɛ3 or ɛ4/ɛ4, n = 38), who were roughly matched to an ɛ3/ɛ3 control by age, sex, and lipid-lowering medication (n = 76). Low density lipoprotein cholesterol levels were genotype dependent (ɛ4/ɛ4> ɛ4/ɛ3> ɛ3/ɛ3> ɛ2/ɛ3> ɛ2/ɛ2).

Comparison of Single Phase and Biphasic Extraction Protocols for Lipidomic Studies Using Human Plasma.

Lipidomic profiling of plasma is an emerging field, given the importance of lipids in major cellular pathways, and is dependent on efficient lipid extraction protocols. Recent attention has turned to plasma lipidomics as a means to identify potential diagnostic and prognostic biomarkers related to dementia, neuropsychiatric health and disease. Although several solvent-based lipid extraction protocols have been developed and are currently in use, novel and more efficient methods could greatly simplify lipid analysis in plasma and warrant investigation.