Your search for: 'author:("Masters, Colin L.")' has returned 68 results. (0.074s) Save search

Authors: Masters, Colin L. | Beyreuther, Konrad

Article Type: Research Article

Abstract: Many participants played a role in discovering the composition and sequence of the Aβ amyloid of Alzheimer's disease. This sequence enabled the cloning of the amyloid precursor protein (APP), which elucidated its proteolytic origin from the membrane of neurons. The proteolytic enzymes which process APP and the Aβ fragment itself are now the prime validated drug targets for therapeutic intervention.

DOI: 10.3233/JAD-2006-9S318

Citation: Journal of Alzheimer's Disease, vol. 9, no. s3, pp. 155-161, 2006

Authors: Masters, Colin L. | Beyreuther, Konrad

Article Type: Research Article

DOI: 10.3233/JAD-2001-3112

Citation: Journal of Alzheimer's Disease, vol. 3, no. 1, pp. 83-86, 2001

Authors: McLean, Catriona A. | Beyreuther, Konrad | Masters, Colin L.

Article Type: Research Article

Abstract: The biogenesis and degradation/clearance of Aβ amyloid lies at the centre of the pathogenesis of Alzheimer's disease. Quantification of the various metabolic pools of Aβ in the brains and in the periphery may aid in diagnosis, prognosis and the elucidation of the natural history of this disorder. Estimation of the Aβ levels using immunoassays (ELISA and the western blots) are complementary techniques which are now being applied in humans and experimental models. The various forms of Aβ in differing cellular compartments are now being assayed, and a picture of the natural history of Alzheimer's disease is beginning to emerge.

DOI: 10.3233/JAD-2001-3305

Citation: Journal of Alzheimer's Disease, vol. 3, no. 3, pp. 305-312, 2001

Authors: Khalil, Zeinab | Poliviou, Helen | Maynard, Christa J. | Beyreuther, Konrad | Masters, Colin L. | Li, Qiao-Xin

Article Type: Research Article

Abstract: Freshly prepared soluble amyloid (Aβ) peptide has been reported to have vascular actions both in vitro and in vivo. This study was designed to examine the in vivo microvascular effects ofβ in two skin microvascular model systems that might reflect possible short and long-term vascular effects of this peptide. Short-term vascular effects were examined using freshly prepared soluble Aβ(1-40) peptide superfused over naive rat skin microvasculature for 15 min. Peripheral microvascular functional changes in 9-months-old transgenic (Tg) mice overexpressing solubleβ in the brain, peripheral circulation and other tissues, were also examined. Microvascular responses were monitored using laser Doppler flowmetry from …the base of a blister raised on the hind footpad of the animals. Endothelial-dependent and independent vasodilatation responses (VD) were examined using acetylcholine (ACh) and sodium nitroprusside (SNP) respectively. The exposure of naïve rat skin microvasculature to Aβ(1-40) resulted in an immediate vasoconstriction (VC) that prevented ACh but not SNP from inducing a subsequent VD response. The vascular effects of Aβ(1-40) were reversed by antioxidants (superoxide dismutase and catalase) and an endothelin A (ETA) receptor antagonist (BQ-123). Tg mice overexpressing soluble Aβ and C100 showed significant reductions in both endothelial-dependent and endothelial-independent VD that were also reversed by antioxidants and BQ-123. In conclusion, this study provided evidence to support the notion of peripheral vascular effects of Aβ in vivo and present novel evidence for alterations in endothelial and smooth muscle cell function in peripheral skin microvasculature in Tg mice overexpressing Aβ and C100. We suggest that skin microvasculature is a useful model to examine the mechanisms underlying the vascular actions of the Aβ protein. Show more

Keywords: Amyloid β-peptide, skin microvasculature, endothelial cell function, endothelin, reactive oxygen species, transgenic mouse, Alzheimer's disease

DOI: 10.3233/JAD-2002-4603

Citation: Journal of Alzheimer's Disease, vol. 4, no. 6, pp. 467-478, 2002

Authors: Villemagne, Victor L. | Pike, Kerryn | Pejoska, Svetlana | Boyd, Alison | Power, Margaret | Jones, Gareth | Masters, Colin L. | Rowe, Christopher C.

Article Type: Short Communication

Abstract: Brain amyloid imaging is becoming an essential tool for the pre-mortem evaluation of Alzheimer's disease (AD). This study explores the pattern of 11 C-PiB retention in a subject with Worster-Drought syndrome (WDS). A 55 year-old male carrier of the WDS gene mutation with mild signs of ataxia and subtle cognitive impairment underwent MRI and 11 C-PiB-PET studies. Brain PiB regional distribution was compared to those from cohorts of healthy controls and AD patients. While no significant cortical 11 C-PiB retention was present, a high degree of cerebellar 11 C-PiB retention was observed in a genetically confirmed carrier of the WDS …gene. We speculate that the sparsity of ABri plaques in the neocortex together with its high deposition in the cerebellum, might explain the observed pattern of 11 C-PiB retention. Show more

Keywords: Amyloid, brain imaging, Familial British Dementia, PiB, positron emission tomography, Worster-Drought syndrome

DOI: 10.3233/JAD-2010-1241

Citation: Journal of Alzheimer's Disease, vol. 19, no. 2, pp. 423-428, 2010

Authors: Bahar-Fuchs, Alex | Chételat, Gael | Villemagne, Victor L. | Moss, Simon | Pike, Kerryn | Masters, Colin L. | Rowe, Christopher | Savage, Greg

Article Type: Research Article

Abstract: Olfactory deficits and increased amyloid-β (Aβ) burden are observed in people with amnestic mild cognitive impairment (aMCI); both factors may be predictive of Alzheimer's disease (AD). We explored whether olfactory identification is related to in vivo measures of Aβ burden using Pittsburgh Compound B (PiB) PET. Nineteen control, 24 aMCI, and 20 AD participants completed an olfactory identification task and underwent PiB PET scanning. Control participants performed better on olfactory identification and showed lower PiB binding than aMCI patients. There was a significant correlation between both factors when pooling all groups together but not when considering each group separately. In …addition, the olfactory identification score did not differ between aMCI participants who were PiB-positive and those who were PiB-negative. We conclude that AD-related olfactory identification deficits are not directly related to Aβ burden. Show more

Keywords: Alzheimer's disease, amyloid-β, diagnosis, mild cognitive impairment, olfaction, PET imaging, Pittsburgh Compound B

DOI: 10.3233/JAD-2010-100696

Citation: Journal of Alzheimer's Disease, vol. 22, no. 4, pp. 1081-1087, 2010

Authors: Watt, Andrew D. | Perez, Keyla A. | Rembach, Alan R. | Masters, Colin L. | Villemagne, Victor L. | Barnham, Kevin J.

Article Type: Research Article

Abstract: Effective therapeutic interventions for Alzheimer's disease (AD) will require treatment regimes to move toward the earliest stages of the disease. For this to occur the field has to identify biomarkers that are able to accurately identify individuals at risk for progression toward AD in the presymptomatic stage. One very significant implication is that some form of population-based screening will need to be undertaken in order to identify those at risk. To date, efforts in neuroimaging brain amyloid-β (Aβ) and changes in cerebrospinal fluid Aβ and tau levels shows promise, however, it is questionable as to whether these methods are applicable …for screening the general population. The Aβ peptide is also found in blood which is the most economical and efficient biological fluid to analyze. Unfortunately, investigations into blood-based diagnostic markers have produced mixed results. This variability is likely to be the result of differences in the preanalytical processing of samples and as such is delaying progress in the field. Reported preanalytical processing techniques from 87 recent articles focusing on the measurement of Aβ in blood were compared, to investigate whether basic sample-handling techniques were comparable between studies. This comparison revealed that not only is it likely that some of the variability in blood-based results is attributable to discrepancies in preanalytical methodologies but also that the field is failing to adequately report sample processing techniques. This review highlights the current shortcomings in methodological reporting and recommends a standardized blood collection methodology based on the limited consensus of the reviewed articles. Show more

Keywords: Alzheimer's disease, amyloid-β, biomarkers, blood, plasma, protocol, standardized

DOI: 10.3233/JAD-2012-120058

Citation: Journal of Alzheimer's Disease, vol. 30, no. 2, pp. 323-336, 2012

Authors: Peters, Kirsten E. | Davis, Wendy A. | Taddei, Kevin | Martins, Ralph N. | Masters, Colin L. | Davis, Timothy M.E. | Bruce, David G.

Article Type: Research Article

Abstract: Background: Plasma amyloid-β (Aβ) levels have rarely been investigated in type 2 diabetes despite its known associations with Alzheimer’s disease. Objective: To compare blood plasma Aβ concentrations (Aβ40 and Aβ42 ) in cognitively normal individuals with and without type 2 diabetes. Methods: Plasma Aβ40 and Aβ42 were measured in 194 participants with diabetes recruited from the community-based Fremantle Diabetes Study Phase II cohort (mean age 71 years, 59% males) and 194 age-, sex-, and APOE ɛ 4 allele-matched, control subjects without diabetes from the Australian Imaging, Biomarkers and Lifestyle Study using a multiplex microsphere-based immunoassay. Results: Plasma Aβ40 and Aβ42 …were normally distributed in the controls but were bimodal in the participants with diabetes. Median Aβ40 and Aβ42 concentrations were significantly lower in those with type 2 diabetes (Aβ40 median [inter-quartile range]: 125.0 [52.6–148.3] versus 149.3 [134.0–165.6] pg/mL; Aβ42 : 26.9 [14.5–38.3] versus 33.6 [28.0–38.9] pg/mL, both p  < 0.001) while the ratio Aβ42 :Aβ40 was significantly higher (0.26 [0.23–0.32] versus 0.22 [0.19–0.25], p  < 0.001). After adjustment, participants with diabetes and plasma Aβ40 levels in the low peak of the bimodal distribution were significantly more likely to have normal to high estimated glomerular filtration rates (odds ratio (95% CI): 2.40 (1.20–4.80), p  = 0.013) although the group with diabetes had lower renal function overall. Conclusion: Type 2 diabetes is associated with altered plasma concentrations of Aβ peptides and is an important source of variation that needs to be taken into account when considering plasma Aβ peptides as biomarkers for Alzheimer’s disease. Show more

Keywords: Alzheimer’s disease, amyloid-β, peptides, blood biomarkers, type 2 diabetes mellitus

DOI: 10.3233/JAD-161050

Citation: Journal of Alzheimer's Disease, vol. 56, no. 3, pp. 1127-1133, 2017

Authors: Sarant, Julia Z. | Harris, David C. | Busby, Peter A. | Fowler, Christopher | Fripp, Jurgen | Masters, Colin L. | Maruff, Paul

Article Type: Research Article

Abstract: Background: Hearing loss is independently associated with a faster rate of cognitive decline in older adults and has been identified as a modifiable risk factor for dementia. The mechanism for this association is unknown, and there has been limited exploration of potential casual pathology. Objective: Our objective was to investigate whether there was an association between degree of audiometrically measured hearing loss (HL) and brain amyloid-β (Aβ) in a pre-clinical sample. Methods: Participants of the Australian Imaging and Biomarker Longitudinal Study (AIBL; n  = 143) underwent positron emission tomography (PET) imaging and objective measurement of hearing thresholds within 5 years of …imaging, as well as cognitive assessment within 2 years of imaging in this observational cohort study. Results: With one exception, study participants who had cognitive assessments within 2 years of their PET imaging (n  = 113) were classified as having normal cognition. There was no association between cognitive scores and degree of hearing loss, or between cognitive scores and Aβ load. No association between HL and Aβ load was found once age was controlled for. As previously reported, positive Apolipoprotein E4 (APOE4 ) carrier status increased the risk of being Aβ positive (p  = 0.002). Conclusion: Degree of HL was not associated with positive Aβ status. Show more

Keywords: Amyloid, cognition, dementia, hearing loss, neuroimaging

DOI: 10.3233/JAD-215121

Citation: Journal of Alzheimer's Disease, vol. 85, no. 1, pp. 359-367, 2022

Authors: Waller, Michael | Buckley, Rachel F. | Masters, Colin L. | Nona, Francis R. | Eades, Sandra J. | Dobson, Annette J.

Article Type: Research Article

Abstract: Background: The prevalence of dementia is generally reported to be higher among Indigenous peoples. Objective: The rates and coding of dementia mortality were compared between Indigenous and non-Indigenous Australians. Methods: De-identified individual records on causes of death for all people aged 40 years or more who died in Australia between 2006 and 2014 (n  = 1,233,084) were used. There were 185,237 records with International Classification of Diseases, Tenth Revision , codes for dementia (Alzheimer’s Disease, vascular dementia, or unspecified dementia) as the underlying cause of death or mentioned elsewhere on the death certificate. Death rates were compared using Poisson regression. Logistic …regression was used to assess whether dementia was more likely to be classified as ‘unspecified’ type in Indigenous Australians. Results: The rates of death with dementia were 57% higher in Indigenous Australians, compared to non-Indigenous, relative rate (RR) 1.57, 95% confidence interval (CI) (1.48, 1.66), p  < 0.0001. This excess of deaths was highest at ages below 75 (RRs > 2, test for interaction p  < 0.0001), and among men (test for interaction p  < 0.0001). When the underreporting of Indigenous status on the death certificate was taken into account the relative rate increased to 2.17, 95% CI (2.07, 2.29). Indigenous Australians were also more likely to have their dementia coded as ‘unspecified’ on their death certificate (Odds Ratio 1.92, 95% CI (1.66, 2.21), p  < 0.0001), compared to the non-Indigenous group. Conclusion: This epidemiological analysis based on population level mortality data demonstrates the higher dementia-related mortality rate for Indigenous Australians especially at younger ages. Show more

Keywords: Alzheimer’s disease, dementia, Indigenous, mortality, population-level studies, rural, unspecified dementia, vascular dementia

DOI: 10.3233/JAD-201175

Citation: Journal of Alzheimer's Disease, vol. 81, no. 4, pp. 1589-1599, 2021