ORCID Profile
0000-0003-4594-8818
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In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Central Nervous System | Pattern Recognition and Data Mining | Medical Devices | Inorganic Chemistry | Bioinorganic Chemistry | Cell Metabolism | Artificial Intelligence and Image Processing | Cell Neurochemistry
Expanding Knowledge in the Information and Computing Sciences | Health and Support Services not elsewhere classified | Expanding Knowledge in the Biological Sciences | Expanding Knowledge in Technology |
Publisher: Wiley
Date: 14-03-2013
DOI: 10.1016/J.JALZ.2012.12.006
Abstract: A practical biomarker is required to facilitate the preclinical diagnosis of Alzheimer's disease (AD). Plasma amyloid beta (Aβ)1-40, Aβ1-42, Aβn-40, and Aβn-42 peptides were measured at baseline and after 18 months in 771 participants from the Australian Imaging Biomarkers and Lifestyle (AIBL) study of aging. Aβ peptide levels were compared with clinical pathology, neuroimaging and neuropsychological measurements. Although inflammatory and renal function covariates influenced plasma Aβ levels significantly, a decrease in Aβ1-42/Aβ1-40 was observed in patients with AD, and was also inversely correlated with neocortical amyloid burden. During the 18 months, plasma Aβ1-42 decreased in subjects with mild cognitive impairment (MCI) and in those transitioning from healthy to MCI. Our findings are consistent with a number of published plasma Aβ studies and, although the prognostic value of in idual measures in any given subject is limited, the diagnostic contribution of plasma Aβ may demonstrate utility when combined with a panel of peripheral biomarkers.
Publisher: American Diabetes Association
Date: 10-05-2014
DOI: 10.2337/DC14-0278
Publisher: Springer Science and Business Media LLC
Date: 25-03-2007
DOI: 10.1038/NSMB1228
Abstract: Gamma-aminobutyric acid (GABA) is synthesized by two isoforms of the pyridoxal 5'-phosphate-dependent enzyme glutamic acid decarboxylase (GAD65 and GAD67). GAD67 is constitutively active and is responsible for basal GABA production. In contrast, GAD65, an autoantigen in type I diabetes, is transiently activated in response to the demand for extra GABA in neurotransmission, and cycles between an active holo form and an inactive apo form. We have determined the crystal structures of N-terminal truncations of both GAD isoforms. The structure of GAD67 shows a tethered loop covering the active site, providing a catalytic environment that sustains GABA production. In contrast, the same catalytic loop is inherently mobile in GAD65. Kinetic studies suggest that mobility in the catalytic loop promotes a side reaction that results in cofactor release and GAD65 autoinactivation. These data reveal the molecular basis for regulation of GABA homeostasis.
Publisher: International Union of Crystallography (IUCr)
Date: 26-08-2004
Publisher: Springer Science and Business Media LLC
Date: 30-04-2013
DOI: 10.1038/MP.2013.40
Abstract: Dementia is a global epidemic with Alzheimer's disease (AD) being the leading cause. Early identification of patients at risk of developing AD is now becoming an international priority. Neocortical Aβ (extracellular β-amyloid) burden (NAB), as assessed by positron emission tomography (PET), represents one such marker for early identification. These scans are expensive and are not widely available, thus, there is a need for cheaper and more widely accessible alternatives. Addressing this need, a blood biomarker-based signature having efficacy for the prediction of NAB and which can be easily adapted for population screening is described. Blood data (176 analytes measured in plasma) and Pittsburgh Compound B (PiB)-PET measurements from 273 participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study were utilised. Univariate analysis was conducted to assess the difference of plasma measures between high and low NAB groups, and cross-validated machine-learning models were generated for predicting NAB. These models were applied to 817 non-imaged AIBL subjects and 82 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) for validation. Five analytes showed significant difference between subjects with high compared to low NAB. A machine-learning model (based on nine markers) achieved sensitivity and specificity of 80 and 82%, respectively, for predicting NAB. Validation using the ADNI cohort yielded similar results (sensitivity 79% and specificity 76%). These results show that a panel of blood-based biomarkers is able to accurately predict NAB, supporting the hypothesis for a relationship between a blood-based signature and Aβ accumulation, therefore, providing a platform for developing a population-based screen.
Publisher: American Diabetes Association
Date: 14-09-2013
DOI: 10.2337/DC13-0229
Abstract: To investigate the associations of metformin, serum vitamin B12, calcium supplements, and cognitive impairment in patients with diabetes. Participants were recruited from the Primary Research in Memory (PRIME) clinics study, the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, and the Barwon region of southeastern Australia. Patients with Alzheimer disease (AD) (n = 480) or mild cognitive impairment (n = 187) and those who were cognitively intact (n = 687) were included patients with stroke or with neurodegenerative diseases other than AD were excluded. Subgroup analyses were performed for participants who had either type 2 diabetes (n = 104) or impaired glucose tolerance (n = 22). Participants with diabetes (n = 126) had worse cognitive performance than participants who did not have diabetes (n = 1,228 adjusted odds ratio 1.51 [95% CI 1.03–2.21]). Among participants with diabetes, worse cognitive performance was associated with metformin use (2.23 [1.05–4.75]). After adjusting for age, sex, level of education, history of depression, serum vitamin B12, and metformin use, participants with diabetes who were taking calcium supplements had better cognitive performance (0.41 [0.19–0.92]). Metformin use was associated with impaired cognitive performance. Vitamin B12 and calcium supplements may alleviate metformin-induced vitamin B12 deficiency and were associated with better cognitive outcomes. Prospective trials are warranted to assess the beneficial effects of vitamin B12 and calcium use on cognition in older people with diabetes who are taking metformin.
Publisher: Wiley
Date: 07-2009
Publisher: Elsevier BV
Date: 09-2023
Publisher: Springer Science and Business Media LLC
Date: 11-03-2019
DOI: 10.1038/S41598-018-37149-7
Abstract: It is increasingly recognized that Alzheimer’s disease (AD) exists before dementia is present and that shifts in amyloid beta occur long before clinical symptoms can be detected. Early detection of these molecular changes is a key aspect for the success of interventions aimed at slowing down rates of cognitive decline. Recent evidence indicates that of the two established methods for measuring amyloid, a decrease in cerebrospinal fluid (CSF) amyloid β 1−42 (A β 1−42 ) may be an earlier indicator of Alzheimer’s disease risk than measures of amyloid obtained from Positron Emission Tomography (PET). However, CSF collection is highly invasive and expensive. In contrast, blood collection is routinely performed, minimally invasive and cheap. In this work, we develop a blood-based signature that can provide a cheap and minimally invasive estimation of an in idual’s CSF amyloid status using a machine learning approach. We show that a Random Forest model derived from plasma analytes can accurately predict subjects as having abnormal (low) CSF A β 1−42 levels indicative of AD risk (0.84 AUC, 0.78 sensitivity, and 0.73 specificity). Refinement of the modeling indicates that only APOEε4 carrier status and four plasma analytes (CGA, A β 1−42 , Eotaxin 3, APOE) are required to achieve a high level of accuracy. Furthermore, we show across an independent validation cohort that in iduals with predicted abnormal CSF A β 1−42 levels transitioned to an AD diagnosis over 120 months significantly faster than those with predicted normal CSF A β 1−42 levels and that the resulting model also validates reasonably across PET A β 1−42 status (0.78 AUC). This is the first study to show that a machine learning approach, using plasma protein levels, age and APOEε4 carrier status, is able to predict CSF A β 1−42 status, the earliest risk indicator for AD, with high accuracy.
Publisher: Oxford University Press (OUP)
Date: 03-01-2007
DOI: 10.1093/NAR/GKL1007
Publisher: WORLD SCIENTIFIC
Date: 02-2007
Publisher: Springer New York
Date: 2012
DOI: 10.1007/978-1-4614-5434-2_3
Abstract: The most well known effect of single amino acid repeat expansion, beyond a certain threshold, is the development of a specific disease, depending on the protein in which the expansion has occurred. For ex le, the expansion of the glutamine repeat in huntingtin leads to the debilitating neurodegenerative disease, Huntington's disease. Similarly, there are a range of other disorders caused by trinucleotide repeat expansions encoding polyglutamine or polyalanine tracts. The age of onset of the polyglutamine-induced neurodegenerative diseases is usually negatively correlated with the length of expanded CAG/glutamine repeat. However, recent studies have given evidence that single amino acid repeats may also play critical roles in normal protein function and that changes in the length of single amino acid repeats is likely to play a beneficial role in evolution. This chapter will look at the prevalence, function and possible role single amino acid repeats have in evolution and other biological processes.
Publisher: IEEE
Date: 2007
Publisher: Cold Spring Harbor Laboratory
Date: 13-06-2007
DOI: 10.1101/GR.6255407
Abstract: Over 3% of human proteins contain single amino acid repeats (repeat-containing proteins, RCPs). Many repeats (homopeptides) localize to important proteins involved in transcription, and the expansion of certain repeats, in particular poly-Q and poly-A tracts, can also lead to the development of neurological diseases. Previous studies have suggested that the homopeptide makeup is a result of the presence of G+C-rich tracts in the encoding genes and that expansion occurs via replication slippage. Here, we have performed a large-scale genomic analysis of the variation of the genes encoding RCPs in 13 species and present these data in an online database ( repeats.med.monash.edu.au/genetic_analysis/ ). This resource allows rapid comparison and analysis of RCPs, homopeptides, and their underlying genetic tracts across the eukaryotic species considered. We report three major findings. First, there is a bias for a small subset of codons being reiterated within homopeptides, and there is no G+C or A+T bias relative to the organism’s transcriptome. Second, single base pair transversions from the homocodon are unusually common and may represent a mechanism of reducing the rate of homopeptide mutations. Third, homopeptides that are conserved across different species lie within regions that are under stronger purifying selection in contrast to nonconserved homopeptides.
Publisher: IEEE
Date: 05-2009
Publisher: Cold Spring Harbor Laboratory
Date: 07-06-2023
DOI: 10.1101/2023.06.05.543705
Abstract: Stemformatics is an established online data portal which hosts hundreds of curated gene expression datasets. It has been serving the stem cell research community for over a decade, by hosting transcriptional profiles of pluripotent and adult stem cells and their progeny from multiple tissues and derivation methods. The portal provides easy-to-use online tools to explore gene expression patterns in published data. In recent years, Stemformatics has shifted its focus from curation to collation and integration of public data with shared phenotypes. It now hosts several integrated expression atlases based on human myeloid cells, which allow for easy cross-dataset comparisons and discovery of emerging cell subsets and activation properties. The inclusion of laboratory-derived cell types enables users to benchmark their own data, to assist with cell-type standardisation or improve cell-derivation methods. The s le annotations have been greatly improved to enable better data integration, and the website has also undergone a major upgrade to modernise its visualisation tools. An application programming interface server also provides the data directly for computational users. Stemformatics is an open-source project and readily available at stemformatics.org.
Publisher: Cold Spring Harbor Laboratory
Date: 04-2021
DOI: 10.1101/GR.3096505
Abstract: Expansion of “low complex” repeats of amino acids such as glutamine (Poly-Q) is associated with protein misfolding and the development of degenerative diseases such as Huntington's disease. The mechanism by which such regions promote misfolding remains controversial, the function of many repeat-containing proteins (RCPs) remains obscure, and the role (if any) of repeat regions remains to be determined. Here, a Web-accessible database of RCPs is presented. The distribution and evolution of RCPs that contain homopeptide repeats tracts are considered, and the existence of functional patterns investigated. Generally, it is found that while polyamino acid repeats are extremely rare in prokaryotes, several eukaryote putative homologs of prokaryote RCP—involved in important housekeeping processes—retain the repetitive region, suggesting an ancient origin for certain repeats. Within eukarya, the most common uninterrupted amino acid repeats are glutamine, asparagines, and alanine. Interestingly, while poly-Q repeats are found in vertebrates and nonvertebrates, poly-N repeats are only common in more primitive nonvertebrate organisms, such as insects and nematodes. We have assigned function to eukaryote RCPs using Online Mendelian Inheritance in Man (OMIM), the Human Reference Protein Database (HRPD), FlyBase, and Wormpep. Prokaryote RCPs were annotated using BLASTp searches and Gene Ontology. These data reveal that the majority of RCPs are involved in processes that require the assembly of large, multiprotein complexes, such as transcription and signaling.
Publisher: Oxford University Press (OUP)
Date: 25-08-2010
DOI: 10.1093/BRAIN/AWQ187
Abstract: β-Amyloid deposition is one of the main hallmarks of Alzheimer's disease thought to eventually cause neuronal death. Post-mortem and neuroimaging studies have consistently reported cases with documented normal cognition despite high β-amyloid burden. It is of great interest to understand what differentiates these particular subjects from those without β-amyloid deposition or with both β-amyloid deposition and cognitive deficits, i.e. what allows these subjects to resist the damage of the pathological lesions. [¹¹C]Pittsburgh compound B positron emission tomography and magnetic resonance brain scans were obtained in 149 participants including healthy controls and patients with subjective cognitive impairment, mild cognitive impairment and Alzheimer's disease. Magnetic resonance data were compared between high versus low-[11C]Pittsburgh compound B cases, and between high-[¹¹C]Pittsburgh compound B cases with versus those without cognitive deficits. Larger temporal (including hippoc al) grey matter volume, associated with better episodic memory performance, was found in high- versus low-[¹¹C]Pittsburgh compound B healthy controls. The same finding was obtained using different [¹¹C]Pittsburgh compound B thresholds, correcting [¹¹C]Pittsburgh compound B data for partial averaging, using age, education, Mini-Mental State Examination, apolipoprotein E4 and sex-matched subs les, and using manual hippoc al delineation instead of voxel-based analysis. By contrast, in participants with subjective cognitive impairment, significant grey matter atrophy was found in high-[¹¹C]Pittsburgh compound B cases compared to low-[¹¹C]Pittsburgh compound B cases, as well as in high-[¹¹C]Pittsburgh compound B cases with subjective cognitive impairment, mild cognitive impairment and Alzheimer's disease compared to high-[¹¹C]Pittsburgh compound B healthy controls. Larger grey matter volume in high-[¹¹C]Pittsburgh compound B healthy controls may reflect either a tissue reactive response to β-amyloid or a combination of higher 'brain reserve' and under-representation of subjects with standard/low temporal volume in the high-[¹¹C]Pittsburgh compound B healthy controls. Our complementary analyses tend to support the latter hypotheses. Overall, our findings suggest that the deleterious effects of β-amyloid on cognition may be delayed in those subjects with larger brain (temporal) volume.
Publisher: Cold Spring Harbor Laboratory
Date: 19-09-2017
DOI: 10.1101/190207
Abstract: It is increasingly recognized that Alzheimer’s disease (AD) exists before dementia is present and that shifts in amyloid beta occur long before clinical symptoms can be detected. Early detection of these molecular changes is a key aspect for the success of interventions aimed at slowing down rates of cognitive decline. Recent evidence indicates that of the two established methods for measuring amyloid, a decrease in cerebral spinal fluid (CSF) amyloid β 1−42 (A β 1−42 ) may be an earlier indicator of Alzheimer’s disease risk than measures of amyloid obtained from Positron Emission Topography (PET). However, CSF collection is highly invasive and expensive. In contrast, blood collection is routinely performed, minimally invasive and cheap. In this work, we develop a blood-based signature that can provide a cheap and minimally invasive estimation of an in idual’s CSF amyloid status using a machine learning approach. We show that a Random Forest model derived from plasma analytes can accurately predict subjects as having abnormal (low) CSF A β 1−42 levels indicative of AD risk (0.84 AUC, 0.78 sensitivity, and 0.73 specificity). Refinement of the modeling indicates that only APOEε4 carrier status and four analytes are required to achieve a high level of accuracy. Furthermore, we show across an independent validation cohort that in iduals with predicted abnormal CSF A β 1−42 levels transitioned to an AD diagnosis over 120 months significantly faster than those predicted with normal CSF A β 1−42 levels and that the resulting model also performs reasonably across PET A β 1−42 status. This is the first study to show that a machine learning approach, using plasma protein levels, age and APOEε4 carrier status, is able to predict CSF A β 1 - 42 status, the earliest risk indicator for AD, with high accuracy.
Publisher: Springer Science and Business Media LLC
Date: 14-01-2014
DOI: 10.1038/MP.2013.178
Abstract: Lower hemoglobin is associated with cognitive impairment and Alzheimer's disease (AD). Since brain iron homeostasis is perturbed in AD, we investigated whether this is peripherally reflected in the hematological and related blood chemistry values from the Australian Imaging Biomarker and Lifestyle (AIBL) study (a community-based, cross-sectional cohort comprising 768 healthy controls (HC), 133 participants with mild cognitive impairment (MCI) and 211 participants with AD). We found that in iduals with AD had significantly lower hemoglobin, mean cell hemoglobin concentrations, packed cell volume and higher erythrocyte sedimentation rates (adjusted for age, gender, APOE-ɛ4 and site). In AD, plasma iron, transferrin, transferrin saturation and red cell folate levels exhibited a significant distortion of their customary relationship to hemoglobin levels. There was a strong association between anemia and AD (adjusted odds ratio (OR)=2.43, confidence interval (CI) (1.31, 4.54)). Moreover, AD emerged as a strong risk factor for anemia on step-down regression, even when controlling for all other available explanations for anemia (adjusted OR=3.41, 95% CI (1.68, 6.92)). These data indicated that AD is complicated by anemia, which may itself contribute to cognitive decline.
Publisher: Springer Science and Business Media LLC
Date: 2005
DOI: 10.1038/NMETH0105-3
Publisher: Oxford University Press (OUP)
Date: 2014
DOI: 10.1039/C3MT00308F
Abstract: The Niemann–Pick type C1 disease protein, NPC1 may have a critical role in transition metal homeostasis.
Publisher: Oxford University Press (OUP)
Date: 2016
DOI: 10.1039/C6MT00019C
Abstract: We examined serum and erythrocyte lead and manganese levels in the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL), which contains over 1000 registrants including over 200 cases of Alzheimer's disease (AD) and 100 mildly cognitively impaired (MCI) in iduals. After correcting for confounding effects of age, collection site and sex, we found a significant decrease in serum manganese levels in AD subjects compared to healthy controls. Analysis of smaller subset of erythrocytes revealed no difference in either lead or manganese levels in AD. Although lead and manganese have neurotoxic effects and may be involved in AD pathology, our results showed that neither metal in serum nor erythrocytes are suitable biomarkers in our cohort. However, prospective studies might reveal whether the burden of either metal modifies disease outcomes.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 14-09-2007
Abstract: Proteins containing membrane attack complex erforin (MACPF) domains play important roles in vertebrate immunity, embryonic development, and neural-cell migration. In vertebrates, the ninth component of complement and perforin form oligomeric pores that lyse bacteria and kill virus-infected cells, respectively. However, the mechanism of MACPF function is unknown. We determined the crystal structure of a bacterial MACPF protein, Plu-MACPF from Photorhabdus luminescens , to 2.0 angstrom resolution. The MACPF domain reveals structural similarity with poreforming cholesterol-dependent cytolysins (CDCs) from Gram-positive bacteria. This suggests that lytic MACPF proteins may use a CDC-like mechanism to form pores and disrupt cell membranes. Sequence similarity between bacterial and vertebrate MACPF domains suggests that the fold of the CDCs, a family of proteins important for bacterial pathogenesis, is probably used by vertebrates for defense against infection.
Publisher: Wiley
Date: 06-2010
Abstract: The primary constituent of the amyloid plaque, beta-amyloid (Abeta), is thought to be the causal "toxic moiety" of Alzheimer's disease. However, despite much work focused on both Abeta and its parent protein, amyloid precursor protein (APP), the functional roles of APP and its cleavage products remain to be fully elucidated. Protein-protein interaction networks can provide insight into protein function, however, high-throughput data often report false positives and are in frequent disagreement with low-throughput experiments. Moreover, the complexity of the CNS is likely to be under represented in such databases. Therefore, we curated the published work characterizing both APP and Abeta to create a protein interaction network of APP and its proteolytic cleavage products, with annotation, where possible, to the level of APP binding domain and isoform. This is the first time that an interactome has been refined to domain level, essential for the interpretation of APP due to the presence of multiple isoforms and processed fragments. Gene ontology and network analysis were used to identify potentially novel functional relationships among interacting proteins.
Publisher: Society for Neuroscience
Date: 05-05-2010
DOI: 10.1523/JNEUROSCI.5180-09.2010
Abstract: Alzheimer's disease (AD) is the most common age-related dementia. Unfortunately due to a lack of validated biomarkers definitive diagnosis relies on the histological demonstration of amyloid-β (Aβ) plaques and tau neurofibrillary tangles. Aβ processing is implicated in AD progression and many therapeutic strategies target various aspects of this biology. While Aβ deposition is the most prominent feature of AD, oligomeric forms of Aβ have been implicated as the toxic species inducing the neuronal dysfunction. Currently there are no methods allowing routine monitoring of levels of such species in living populations. We have used surface enhanced laser desorption ionization time of flight (SELDI-TOF) mass spectrometry incorporating antibody capture to investigate whether the cellular membrane-containing fraction of blood provides a new source of biomarkers. There are significant differences in the mass spectra profiles of AD compared with HC subjects, with significantly higher levels of Aβ monomer and dimer in the blood of AD subjects. Furthermore, levels of these species correlated with clinical markers of AD including brain Aβ burden, cognitive impairment and brain atrophy. These results indicate that fundamental biochemical events relevant to AD can be monitored in blood, and that the species detected may be useful clinical biomarkers for AD.
Publisher: S. Karger AG
Date: 2011
DOI: 10.1159/000325171
Abstract: i Background/Aims: /i The nature and extent of adverse cognitive effects due to the prescription of anticholinergic drugs in older people with and without dementia is unclear. i Methods: /i We calculated the anticholinergic load (ACL) of medications taken by participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing, a cohort of 211 Alzheimer’s disease (AD) patients, 133 mild cognitive impairment (MCI) patients and 768 healthy controls (HC) all aged over 60 years. The association between ACL and cognitive function was examined for each diagnostic group (HC, MCI, AD). i Results: /i A high ACL within the HC group was associated with significantly slower response speeds for the Stroop color and incongruent trials. No other significant relationships between ACL and cognition were noted. i Conclusion: /i In this large cohort, prescribed anticholinergic drugs appeared to have modest effects upon psychomotor speed and executive function, but not on other areas of cognition in healthy older adults.
Publisher: Cold Spring Harbor Laboratory
Date: 15-04-2022
DOI: 10.1101/2022.04.14.488416
Abstract: Creating and curating knowledge resources has been a paramount activity in the biomedical domain. In recent years, automated methods for knowledge base construction have flourished and have enabled large scale construction and curation of such resources. In the biological domain, techniques such as next generation sequencing produce new data at exponential rate, making mere manual curation of knowledge resources simply unfeasible. The major technology to automate knowledge base construction is Information Extraction — specifically tasks such as Named Entity Recognition or Relation Extraction. The major hurdle for IE methods is the availability of labelled data for training, which can be prohibitively expensive and challenging to obtain due to the need of domain experts. Active learning aims at minimizing the cost of manual labelling by only requiring it for smaller and more useful portions of the data. With this motivation, we devised a method to quickly construct highly curated datasets to enable biomedical knowledge base construction. The method, named BioAct , is based on a partnership between automatic annotation methods (leveraging SciBERT with other machine learning models) and subject matter experts and uses active learning to create training datasets in the biological domain. The main contribution of this work is twofold in addition to the BioAct method itself, we publicly release an annotated dataset on antimicrobial resistance, produced by a team of subject matter experts using BioAct . Additionally, we simulate a knowledge base construction task using the MegaRes and CARD knowledge bases to provide insight and lessons learned about the usefulness of the annotated dataset for this task.
Publisher: Springer Science and Business Media LLC
Date: 19-05-2015
DOI: 10.1038/NCOMMS7760
Abstract: Brain iron elevation is implicated in Alzheimer’s disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. Ferritin was strongly associated with CSF apolipoprotein E levels and was elevated by the Alzheimer’s risk allele, APOE-ɛ4 . These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-ɛ4 being the major genetic risk factor for AD.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-08-2016
DOI: 10.1212/WNL.0000000000003094
Abstract: We assessed a blood-based signature, which previously demonstrated high accuracy at stratifying in iduals with high or low neocortical β-amyloid burden (NAB), to determine whether it could also identify in iduals at risk of progression to Alzheimer disease (AD) within 54 months. We generated the blood-based signature for 585 healthy controls (HCs) and 74 participants with mild cognitive impairment (MCI) from the Australian Imaging, Biomarkers and Lifestyle Study who underwent clinical reclassification (blinded to biomarker findings) at 54-month follow-up. The in iduals were split into estimated high and low NAB groups based on a cutoff of 1.5 standardized uptake value ratio. We assessed the predictive accuracy of the high and low NAB groupings based on progression to mild cognitive impairment or AD according to clinical reclassification at 54-month follow-up. Twelve percent of HCs with estimated high NAB progressed in comparison to 5% of HCs with estimated low NAB (odds ratio = 2.4). Forty percent of the participants with MCI who had estimated high NAB progressed in comparison to 5% of the participants with MCI who had estimated low NAB (odds ratio = 12.3). These ratios are in line with those reported for Pittsburgh compound B–PET results. In iduals with estimated high NAB had faster rates of memory decline than those with estimated low NAB. These findings suggest that a simple blood-based signature not only provides estimates of NAB but also predicts cognitive decline and disease progression, identifying in iduals at risk of progressing toward AD at the prodromal and preclinical stages.
Publisher: American Medical Association (AMA)
Date: 10-2012
Publisher: Wiley
Date: 07-2011
Publisher: Wiley
Date: 07-2016
Publisher: Wiley
Date: 07-2016
Publisher: Wiley
Date: 14-11-2006
DOI: 10.1002/PROT.20776
Abstract: The crystallization of macromolecules remains a major bottleneck in structural biology. The routine screening of more than one thousand crystallization conditions and subsequent optimization by fine screening presents a challenge to conventional laboratory notebook keeping. In addition, the development of high-throughput robotic crystallization and imaging systems presents a pressing need for low-cost laboratory information management system (LIMS). Here we describe CLIMS2, a crystallization LIMS that features a simple, user-friendly graphical interface, allowing the storage, management, retrieval and mining of crystallization data. The CLIMS2 executable and documentation is freely available at clims.med.monash.edu.au.
Location: Australia
Start Date: 2016
End Date: 2018
Funder: Australian Research Council
View Funded ActivityStart Date: 2017
End Date: 2021
Funder: Australian Research Council
View Funded ActivityStart Date: 06-2018
End Date: 12-2024
Amount: $4,133,659.00
Funder: Australian Research Council
View Funded ActivityStart Date: 01-2016
End Date: 01-2019
Amount: $348,500.00
Funder: Australian Research Council
View Funded Activity