| 1. |
- Choo, Il Han, et al.
(författare)
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Combination of f 18 fdg pet and cerebrospinal fluid biomarkers as a better predictor of the progression to alzheimer's disease in mild cognitive impairment patients
- 2013
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 33:4, s. 929-939
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Tidskriftsartikel (refereegranskat)abstract
- The biomarker-based new diagnostic criteria have been proposed for Alzheimer's disease (AD) spectrum. However, any biomarker alone has not been known to have satisfactory AD predictability. We explored the best combination model with baseline demography, neuropsychology, F-18-fluorodeoxyglucose positron emission tomography (FDG-PET), cerebrospinal fluid (CSF) biomarkers, and apolipoprotein E (APOE) genotype evaluation to predict progression to AD in mild cognitive impairment (MCI) patients. Alongitudinal clinical follow-up (mean, 44 months; range, 1.6-161.7 months) of MCI patients was done. Among 83 MCI patients, 26 progressed to AD (MCI-AD) and 51 did not deteriorate (MCI-Stable). We applied that univariate and multivariate logistic regression analyses, and multistep model selection for AD predictors including biomarkers. In univariate logistic analysis, we selected age, Rey Auditory Verbal Retention Test, parietal glucose metabolic rate, CSF total tau, and presence or not of at least one APOE epsilon 4 allele as predictors. Through multivariate stepwise logistic analysis and model selection, we found the combination of parietal glucose metabolic rate and total tau representing the best model for AD prediction. In conclusion, our findings highlight that the combination of regional glucose metabolic assessment by PET and CSF biomarkers evaluation can significantly improve AD predictive diagnostic accuracy of each respective method.
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| 2. |
- Ni, Ruiqing, et al.
(författare)
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Amyloid tracers binding sites in autosomal dominant and sporadic Alzheimer's disease
- 2017
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 13:4, s. 419-430
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Amyloid imaging has been integrated into diagnostic criteria for Alzheimer's disease (AD). How amyloid tracers binding differ for different tracer structures and amyloid-beta aggregates in autosomal dominant AD (ADAD) and sporadic AD is unclear. Methods: Binding properties of different amyloid tracers were examined in brain homogenates from six ADAD with APPswe, PS1 M146V, and PS1 E Delta 9 mutations, 13 sporadic AD, and 14 control cases. Results: H-3-PIB, H-3-florbetaben, H-3-AZD2184, and BTA-1 shared a high-and a varying low-affinity binding site in the frontal cortex of sporadic AD. AZD2184 detected another binding site (affinity 33 nM) in the frontal cortex of ADAD. The H-3-AZD2184 and H-3-PIB binding were significantly higher in the striatum of ADAD compared to sporadic AD and control. Polyphenol resveratrol showed strongest inhibition on H-3-AZD84 binding followed by H-3-florbetaben and minimal on H-3-PIB. Discussion: This study implies amyloid tracers of different structures detect different sites on amyloid-beta fibrils or conformations.
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| 3. |
- Ni, Ruiqing, et al.
(författare)
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Detection of cerebral tauopathy in P301L mice using high-resolution large-field multifocal illumination fluorescence microscopy
- 2020
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Ingår i: Biomedical Optics Express. - : OPTICAL SOC AMER. - 2156-7085. ; 11:9, s. 4989-5002
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Tidskriftsartikel (refereegranskat)abstract
- Current intravital microscopy techniques visualize tauopathy with high-resolution, but have a small field-of-view and depth-of-focus. Herein, we report a transcranial detection of tauopathy over the entire cortex of P301L tauopathy mice using large-field multifocal illumination (LMI) fluorescence microscopy technique and luminescent conjugated oligothiophenes. In vitro assays revealed that fluorescent ligand h-FTAA is optimal for in vivo tau imaging, which was confirmed by observing elevated probe retention in the cortex of P301L mice compared to non-transgenic littermates. Immunohistochemical staining further verified the specificity of h-FTAA to detect tauopathy in P301L mice. The new imaging platform can be leveraged in pre-clinical mechanistic studies of tau spreading and clearance as well as longitudinal monitoring of tau targeting therapeutics. (C) 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
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| 4. |
- Ni, Ruiqing
(författare)
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Multiple amyloid binding sites in Alzheimer brain and their interaction with synaptic and inflammatory mechanisms
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Alzheimer’s disease (AD) is the most common type of dementia. A series of pathophyslogical changes start many years prior to the emergence of clinical symptoms. The main aims of this thesis were to investigate fibrillar amyloid-β _imaging tracers that bind to the AD brain and the relationships between amyloid pathology, inflammation, and synaptic changes in AD. Amyloid-β _plaque deposition is one of the pathological hallmarks of AD. We demonstrated that amyloid positron emission tomography (PET) tracers 3H-Pittsburgh compound B (PIB), BTA-1, florbetaben, florbetapir and AZD2184 detect a similar high-affinity site and a varying low-affinity binding site on fibrillar amyloid-β _in postmortem sporadic AD brain. Autosomal dominant AD showed an additional binding site with AZD2184 in the frontal cortex and higher 3H-PIB binding in the striatum than in sporadic AD. Amyloid tracer binding to fibrillar Aβ _was influenced by resveratrol and AZD2184 showed the greatest changes. These findings suggest a multiple binding site model for amyloid tracers in the AD brain (Papers I, II). Inflammation is recognized to play a crucial role in AD. Cross-sectional microPET imaging in APPswe transgenic AD mice showed increased 11C-deuterium-L-deprenyl PET binding (astrocytosis) at 6 months compared to age-matched wild-type mice, prior to the increase in 11C-AZD2184 PET retention (amyloid-β _plaque deposition) that occurred at 18-24 months, suggesting that astrocytosis is an early event in comparison to amyloid-β _plaque deposition. In vitro autoradiography and immunochemistry staining confirmed age-related increases in Aβ deposits and indicated a context-dependent astrocytosis in transgenic AD mice (Paper III). Mild cognitive impairment is prodromal stage of AD. We found that the combination of measurement of parietal glucose metabolism using the neurodegeneration biomarker 18F-fluorodeoxyglucose PET with analysis of total tau levels in cerebrospinal fluid provided the best prediction of patients with mild cognitive impairment converting to AD (Paper IV). Aβ assemblies bind to α7_ _nicotinic acetylcholine receptors (nAChRs) and form complexes in the AD brain. 3H-PIB measurements showed increased fibrillar Aβ _levels in the presence of α7 nAChR agonists, suggesting a specific interaction between fibrillar amyloid-β _and α7 nAChRs, and α7 nAChR drugs may influence on the fibrillar Aβ-α7 nAChR interaction (Paper V). In conclusion, clinical amyloid tracers detect multiple binding sites on fibrillar amyloid-β _in the AD brain. Amyloid-β _interacts with astrocytosis and synaptic sites. A deeper understanding of the subtle difference of amyloid-β _binding sites in brain could facilitate the development of amyloid-β _tracers and drugs for AD.
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| 5. |
- Ni, Ruiqing, et al.
(författare)
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Multiscale optical and optoacoustic imaging of amyloid-beta deposits in mice
- 2022
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Ingår i: Nature Biomedical Engineering. - : NATURE PORTFOLIO. - 2157-846X. ; 6, s. 1031-1044
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Tidskriftsartikel (refereegranskat)abstract
- Large-field multifocal illumination fluorescence microscopy and panoramic volumetric multispectral optoacoustic tomography can be combined to longitudinally assess amyloid-beta deposits in transgenic mouse models of Alzheimers disease. Deposits of amyloid-beta (A beta) in the brains of rodents can be analysed by invasive intravital microscopy on a submillimetre scale, or via whole-brain images from modalities lacking the resolution or molecular specificity to accurately characterize A beta pathologies. Here we show that large-field multifocal illumination fluorescence microscopy and panoramic volumetric multispectral optoacoustic tomography can be combined to longitudinally assess A beta deposits in transgenic mouse models of Alzheimers disease. We used fluorescent A beta-targeted probes (the luminescent conjugated oligothiophene HS-169 and the oxazine-derivative AOI987) to transcranially detect A beta deposits in the cortex of APP/PS1 and arcA beta mice with single-plaque resolution (8 mu m) and across the whole brain (including the hippocampus and the thalamus, which are inaccessible by conventional intravital microscopy) at sub-150 mu m resolutions. Two-photon microscopy, light-sheet microscopy and immunohistochemistry of brain-tissue sections confirmed the specificity and regional distributions of the deposits. High-resolution multiscale optical and optoacoustic imaging of A beta deposits across the entire brain in rodents thus facilitates the in vivo study of A beta accumulation by brain region and by animal age and strain.
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