Your search for: 'author:("Bates, Kristyn A.")' has returned 8 results. (0.012s) Save search

Authors: Yang, Jing | Ji, Yong | Mehta, Pankaj | Bates, Kristyn A. | Sun, Yanjie | Wisniewski, Thomas

Article Type: Research Article

Abstract: The accumulation of amyloid-β (Aβ) peptides as toxic oligomers, amyloid plaques, and cerebral amyloid angiopathy (CAA) is critical in the pathogenesis of Alzheimer's disease (AD). The binding of Aβ peptides to apolipoprotein E (ApoE) plays an important role in modulation of amyloid deposition and clearance. We have shown that blocking the Aβ/ApoE interaction with Aβ12-28P , a nontoxic blood-brain-barrier permeable and non-fibrillogenic synthetic peptide, constitutes a novel therapeutic approach for AD by reducing Aβ parenchymal deposition. In the present study, we investigate this therapeutic effect on CAA in the transgenic (Tg) AD mice model (TgSwDI), which expresses Swedish (K670N/M671L), Dutch …(E693Q)/Iowa (D694N) AβPP mutations. These mice develop abundant CAA beginning at the age of 6 months. Behavioral results show that A12-28P treated TgSwDI AD mice performed the same as wild-type mice, whereas vehicle treated TgSwDI were impaired in spatial memory. Furthermore, this treatment resulted in a significant reduction of total amyloid burden, especially the fibrillar vascular amyloid burden, which importantly was accompanied by a reduction in microhemorrhages and neuroinflammation. Measurement of Aβ levels in the brain homogenate revealed a significant decrease in both the total amount of Aβ and Aβ oligomer levels in A12-28P treated TgSwDI mice. These findings suggest that blocking the Aβ/ApoE interaction is a highly effective therapeutic approach for vascular amyloid deposition, in contrast to some other therapeutic approaches. Show more

Keywords: Alzheimer's disease, amyloid-β, apolipoprotein E, cerebral amyloid angiopathy, microhemorrhages, microglia, neuroinflammation

DOI: 10.3233/JAD-2011-101401

Citation: Journal of Alzheimer's Disease, vol. 24, no. 2, pp. 269-285, 2011

Authors: Bates, Kristyn A. | Drummond, Eleanor S. | Cozens, Greg S. | Harvey, Alan R.

Article Type: Research Article

Abstract: Purpose: There is considerable variability in the extent and nature of the glial response to injury and neurodegeneration. Transplantation of fetal cortical tissue onto the brain of neonatal host rats or mice results in region-specific changes dependent on where the fetal tissue is placed. These changes include chronic astrocytic and microglial gliosis, oxidative stress, and altered metabolism of a number of proteins associated with the pathogenesis of Alzheimer’s disease. Such changes are only observed in heterotopic (cortex-to-midbrain) grafts and are not observed in homotopic cortex-to-cortex grafts. We investigated two possible triggers for the region-specific gliosis observed in our transplant model …hypothesizing that either i) poor vascularization and lack of blood brain barrier integrity or ii) an inflammatory response initiated by the transplantation process, contributed to establishing chronic pathological changes. Methods: We analyzed the time course of neovascularization, blood brain barrier permeability and inflammation using a combination of immunohistochemistry, enzyme-linked immunosorbant assay and Evan’s blue dye extravasation techniques. Results: Blood brain barrier permeability and altered neovascularization occurred prior to the onset of gliosis in heterotopic grafts. Conclusion: These data suggest that ischemic conditions and blood brain barrier damage can be a primary mechanism that initiates chronic gliosis and associated inflammatory changes in central nervous system tissue. Show more

Keywords: Astrocytes, transplantation, inflammation, blood brain barrier, gliosis, neovascularization

DOI: 10.3233/RNN-150591

Citation: Restorative Neurology and Neuroscience, vol. 34, no. 2, pp. 313-323, 2016

Authors: Sohrabi, Hamid R. | Bates, Kristyn A. | Rodrigues, Mark | Taddei, Kevin | Martins, Georgia | Laws, Simon M. | Lautenschlager, Nicola T. | Dhaliwal, Satvinder S. | Foster, Jonathan K. | Martins, Ralph N.

Article Type: Research Article

Abstract: Apolipoprotein E ε4 (APOE-ε4) is a major genetic risk factor for Alzheimer's disease. In this study, we addressed the question of whether possession of the APOE-ε4 allele results in adverse effects on perceived health-related quality of life (HRQL) and on symptoms of depression and anxiety in people with subjective memory complaints (SMC). 138 healthy, community-dwelling elderly volunteers, aged 52 to 85, were assessed for HRQL, depression, and anxiety. The participants were classified as i) APOE-ε4 carriers or ii) non-carriers with a) SMC or b) without memory complaints. The possible interactions of APOE genotype, gender, and SMC on HRQL, depression, and …anxiety were investigated statistically. SMC was significantly associated with poorer outcomes on measures of depression, trait anxiety, and mental health. APOE-ε4 carriers did not significantly differ from non-carriers on HRQL, depression, and anxiety. However, significant interaction was found between APOE-ε4 genotype and SMC on depression. These findings are important from a health perspective and suggest that memory complaints are associated with markers of mental health and quality of life that are independent of possession of the APOE-ε4 allele, despite the importance of this polymorphism in the risk of AD and other health problems. Show more

Keywords: Alzheimer's disease, anxiety, APOE-ε4, depression, health-related quality of life (HRQL), subjective memory complaints

DOI: 10.3233/JAD-2009-1018

Citation: Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 69-79, 2009

Authors: Clarke, Darren | Penrose, Marissa A. | Penstone, Tamasin | Fuller-Carter, Paula I. | Hool, Livia C. | Harvey, Alan R. | Rodger, Jennifer | Bates, Kristyn A.

Article Type: Research Article

Abstract: Background: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that uses magnetic pulses over the cranium to induce electrical currents in underlying cortical tissue. Although rTMS has shown clinical utility for a number of neurological conditions, we have only limited understanding of how rTMS influences cellular function and cell-cell interactions. Objective: In this study, we sought to investigate whether repeated magnetic stimulation (rMS) can influence astrocyte biology in vitro . Method: We tested four different rMS frequencies and measured the calcium response in primary neonatal astrocyte cultures. We also tested the effect of rMS on astrocyte migration and proliferation …in vitro . We tested 3 to 4 culture replicates and 17 to 34 cells for each rMS frequency (sham, 1 Hz, cTBS, 10 Hz and biomemetic high frequency stimulation - BHFS). Results: Of all frequencies tested, 1 Hz stimulation resulted in a statistically significant rise in intracellular calcium in the cytoplasmic and nuclear compartments of the cultured astrocytes. This calcium rise did not affect migration or proliferation in the scratch assay, though astrocyte hypertrophy was reduced in response to 1 Hz rMS, 24 hours post scratch injury. Conclusion: Our results provide preliminary evidence that rMS can influence astrocyte physiology, indicating the potential for a novel mechanism by which rTMS can influence brain activity. Show more

Keywords: Astrocytes, repetitive transcranial magnetic stimulation, calcium signalling, injury

DOI: 10.3233/RNN-160708

Citation: Restorative Neurology and Neuroscience, vol. 35, no. 6, pp. 557-569, 2017

Authors: Sohrabi, Hamid R. | Bates, Kristyn A. | Rodrigues, Mark | Taddei, Kevin | Laws, Simon M. | Lautenschlager, Nicola T. | Dhaliwal, Satvinder S. | Johnston, Amy N.B. | Mackay-Sim, Alan | Gandy, Samuel | Foster, Jonathan K. | Martins, Ralph N.

Article Type: Research Article

Abstract: Olfactory dysfunction has been reported in clinical and preclinical phases of Alzheimer's disease. Subjective memory complaints have been proposed as a potential early indicator for increased risk of Alzheimer's disease, but have also been associated with depression, personality characteristics, and health problems. In this study, we aimed to determine which of these putative markers can predict memory complaints in community-dwelling elderly individuals, focusing on olfactory symptoms. A cohort of 144 elderly volunteers (42 males and 102 females), aged 50 to 86, was recruited from an ongoing longitudinal study. Participants were assessed for olfactory capacities (threshold, discrimination, and identification), subjective memory …complaints, depression, and cognitive functions. Subjective memory complaints were significantly associated with olfactory discrimination and identification but not with threshold. Olfactory functions and depressive symptoms were both significantly associated with subjective memory complaints. In addition, memory complainers were significantly worse than non-complainers with respect to olfactory discrimination, identification, and overall olfactory functioning. The findings suggest that olfactory capacity may be a potentially significant biomarker for identifying community-dwelling elderly with memory complaints who are at increased risk for age-related cognitive decline and Alzheimer's disease. Show more

Keywords: Alzheimer's disease, cognitive decline, depression symptoms, olfactory dysfunction, smell identification, Sniffin' Sticks, subjective memory complaints

DOI: 10.3233/JAD-2009-1020

Citation: Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 135-142, 2009

Authors: Rimajova, Mira | Lenzo, Nat P. | Wu, Jing-Shan | Bates, Kristyn A. | Campbell, Andrew | Dhaliwal, Satvinder S. | McCarthy, Michael | Rodrigues, Mark | Paton, Athena | Rowe, Christopher | Foster, Jonathan K. | Martins, Ralph N.

Article Type: Research Article

Abstract: Apolipoprotein E-ϵ4 (APOEε4) has been associated with increased risk of developing Alzheimer's disease (AD) and regional cerebral glucose hypometabolism, as measured by fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET). We report here preliminary data from studies that aim to determine whether cerebral glucose hypometabolism is observed in APOEε4 positive, cognitively intact individuals between the ages of 50 and 80, and whether there is an additional impact of subjective memory complainer (SMC) status on glucose metabolism determined by NeuroStat analysis. FDG-PET was conducted in 30 community dwelling, APOE-ε4 carriers without clinical evidence of dementia and objective cognitive impairment as assessed using a neuropsychological battery. …Neurological soft-signs (NSS) were also assessed. Glucose hypometabolism was demonstrated in the anterior and posterior cingulate cortex and in the temporal association cortices in APOEε4 carriers compared to the normative NeuroStat database. This pattern was particularly evident in APOEε4 heterozygous individuals. SMC showed hypometabolism in the aforementioned brain regions, whereas non-SMC showed no significant pattern of glucose hypometabolism. FDG-PET with NeuroStat analysis showed that APOEε4 carriers have mild glucose hypometabolism in areas associated with AD. SMC may be associated with AD-related differences in regional cerebral glucose metabolism. These findings are currently being investigated in a larger group of APOEε4 carriers. Show more

Keywords: Alzheimer's disease, apolipoprotein E, cognitive aging, FDG-PET, memory

DOI: 10.3233/JAD-2008-13203

Citation: Journal of Alzheimer's Disease, vol. 13, no. 2, pp. 137-146, 2008

Authors: Gardener, Samantha L. | Sohrabi, Hamid R. | Shen, Kai-kai | Rainey-Smith, Stephanie R. | Weinborn, Michael | Bates, Kristyn A. | Shah, Tejal | Foster, Jonathan K. | Lenzo, Nat | Salvado, Olivier | Laske, Christoph | Laws, Simon M. | Taddei, Kevin | Verdile, Giuseppe | Martins, Ralph N.

Article Type: Research Article

Abstract: Increasing evidence suggests that Alzheimer’s disease (AD) sufferers show region-specific reductions in cerebral glucose metabolism, as measured by [18 F]-fluoro-2-deoxyglucose positron emission tomography (18 F-FDG PET). We investigated preclinical disease stage by cross-sectionally examining the association between global cognition, verbal and visual memory, and 18 F-FDG PET standardized uptake value ratio (SUVR) in 43 healthy control individuals, subsequently focusing on differences between subjective memory complainers and non-memory complainers. The 18 F-FDG PET regions of interest investigated include the hippocampus, amygdala, posterior cingulate, superior parietal, entorhinal cortices, frontal cortex, temporal cortex, and inferior parietal region. In the cohort as a whole, …verbal logical memory immediate recall was positively associated with 18 F-FDG PET SUVR in both the left hippocampus and right amygdala. There were no associations observed between global cognition, delayed recall in logical memory, or visual reproduction and 18 F-FDG PET SUVR. Following stratification of the cohort into subjective memory complainers and non-complainers, verbal logical memory immediate recall was positively associated with 18 F-FDG PET SUVR in the right amygdala in those with subjective memory complaints. There were no significant associations observed in non-memory complainers between 18 F-FDG PET SUVR in regions of interest and cognitive performance. We observed subjective memory complaint-specific associations between 18 F-FDG PET SUVR and immediate verbal memory performance in our cohort, however found no associations between delayed recall of verbal memory performance or visual memory performance. It is here argued that the neural mechanisms underlying verbal and visual memory performance may in fact differ in their pathways, and the characteristic reduction of 18 F-FDG PET SUVR observed in this and previous studies likely reflects the pathophysiological changes in specific brain regions that occur in preclinical AD. Show more

Keywords: Brain glucose metabolism, cognition, 18F-FDG PET, subjective memory complaints, verbal memory, visual memory

DOI: 10.3233/JAD-151084

Citation: Journal of Alzheimer's Disease, vol. 52, no. 2, pp. 661-672, 2016

Authors: Bates, Kristyn A. | Sohrabi, Hamid R. | Rodrigues, Mark | Beilby, John | Dhaliwal, Satvinder S. | Taddei, Kevin | Criddle, Arthur | Wraith, Megan | Howard, Matthew | Martins, Georgia | Paton, Athena | Mehta, Pankaj | Foster, Jonathan K. | Martins, Ian J. | Lautenschlager, Nicola T. | Mastaglia, Frank L. | Laws, Simon M. | Gandy, Samuel E. | Martins, Ralph N.

Article Type: Research Article

Abstract: A strong link is indicated between cardiovascular disease (CVD) and risk for developing Alzheimer's disease (AD), which may be exacerbated by the major AD genetic risk factor apolipoprotein Eε4 (APOEε4). Since subjective memory complaint (SMC) may potentially be an early indicator for cognitive decline, we examined CVD risk factors in a cohort of SMC. As amyloid-ε (Aβ) is considered to play a central role in AD, we hypothesized that the CVD risk profile (increased LDL, reduced HDL, and increased body fat) would be associated with plasma Aβ levels. We explored this in 198 individuals with and without SMC (average age …= 63 years). Correlations between Aβ40 and HDL were observed, which were stronger in non-APOEε4 carriers (rho = −0.315, p < 0.001) and in SMC (rho = −0.322, p = 0.01). There was no relationship between percentage body fat and Aβ40 in this cohort. Age and HDL remained predictive for plasma Aβ40 using multivariate regression analysis. We report a novel negative association between HDL and Aβ, which if demonstrated to be causal has implications for the development of lifestyle interventions and/or novel therapeutics. The relationship between HDL and Aβ and the potential significance of such an association needs to be validated in a larger longitudinal study. Show more

Keywords: Aging, amyloid-β, apolipoprotein E, cholesterol, dementia, high density lipoprotein

DOI: 10.3233/JAD-2009-1050

Citation: Journal of Alzheimer's Disease, vol. 17, no. 2, pp. 305-318, 2009