Visual-Statistical Interpretation of 18F-FDG-PET Images for Characteristic Alzheimer Patterns in a Multicenter Study: Inter-Rater Concordance and Relationship to Automated Quantitative Evaluation

Yamane, Toshimi; Ikari, Yasuhiko; Nishio, Tomoyuki; Ishii, Kazunari; Kato, Takashi; Ito, Kengo; Silverman, Daniel; Senda, Michio; Asada, Takashi; Arai, Hiroyuki; Sugishita, Morihiro; Iwatsubo, Takeshi

doi:10.3174/ajnr.a3665

Cited by 42 publications

(29 citation statements)

References 17 publications

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“…Furthermore, oxidative stress is well accepted as a key pathological event that contributes to AD pathogenesis, and is closely linked to induction of neuroinflammation in AD [65–68]. For instance, a number of studies have found that increased ROS accumulation within mitochondria can feedback and facilitate mitochondrial dysfunction, leading to structural damage to the electron transfer chain and resultant ATP synthesis failure [69–71]. In fact, impaired oxidative phosphorylation and decreased ATP generation have been observed in the brains of AD patients, and is viewed as a sensitive index for monitoring cognitive alteration in AD progression [72–74].…”

Section: Discussionmentioning

confidence: 99%

“…In fact, oxidative imbalance leading to a buildup of damaging oxidative byproducts has been consistently reported in AD progression, even at the early stage before significant senile plaques have formed [19–21]. Furthermore, ROS accumulation in mitochondria causes a subsequent destruction of the electron transfer chain that leads to metabolic energy failure and mitochondrial dysfunction [22–24], which have a well-documented role in AD pathology [25, 26]. …”

Section: Introductionmentioning

confidence: 99%

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Treadmill Exercise Exerts Neuroprotection and Regulates Microglial Polarization and Oxidative Stress in a Streptozotocin-Induced Rat Model of Sporadic Alzheimer’s Disease

Dong

Tucker

et al. 2017

JAD

179

103

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Recent work has suggested that exercise may be beneficial in preventing or ameliorating symptoms of several neurological disorders, although the mechanism is not entirely understood. The current study was designed to examine the potential beneficial effect of treadmill exercise upon cognitive function in a streptozotocin (STZ)-induced rat model of Alzheimer’s disease (AD). Animals underwent treadmill exercise (30 min/day, 5 days/week) for 4 weeks after bilateral STZ intracerebroventricular injection (2.4 mg/kg). We demonstrated that treadmill exercise significantly attenuated STZ-induced neurodegeneration in the rat hippocampal CA1 region and strongly preserved hippocampal-dependent cognitive functioning. Further mechanistic investigation displayed a marked suppression of STZ-induced amyloid-β accumulation and tau phosphorylation. Intriguingly, treadmill exercise remarkably inhibited reactive gliosis following STZ insult and effectively shifted activated microglia from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype, which was correlated with a significantly reduced expression of pro-inflammatory mediators and a corresponding enhancement of anti-inflammatory cytokine expression in the hippocampus. Furthermore, treadmill exercise caused a robust suppression of oxidative damage as evidenced by significantly reduced peroxynitrite production, lipid peroxidation, and oxidized DNA damage. Finally, treadmill exercise strongly attenuated STZ-induced mitochondrial dysfunction manifested by a dramatically elevated intra-mitochondrial cytochrome c oxidase activity and ATP synthesis, and markedly inhibited neuronal apoptosis in the hippocampus. These findings demonstrate that treadmill exercise has a multifactorial effect to attenuate many of the pathological processes that play a key role in AD, and provide further support for the beneficial role of exercise as a potential therapeutic option in AD treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Treadmill Exercise Exerts Neuroprotection and Regulates Microglial Polarization and Oxidative Stress in a Streptozotocin-Induced Rat Model of Sporadic Alzheimer’s Disease

Dong

Tucker

et al. 2017

JAD

179

103

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“…Neuronal mitochondrial dysfunction is an early and prominent feature of AD (Wang 2009) as is reduced energy metabolism in the AD brain (Landau 2011, Shokouhi 2013, Yamane 2013). Diminished neuronal expression of genes encoding subunits of the ETC, as well as decreased expression or activity of many enzymes involved in oxidative metabolism, are also well-documented in AD brains (Cottrell 2001, Gibson 1998, Nagy 1999, Parker 1994).…”

Section: Discussionmentioning

confidence: 99%

Alterations in mitochondrial number and function in Alzheimer’s disease fibroblasts

Gray

Quinn

2015

Metab Brain Dis

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Introduction Mitochondrial dysfunction is observed in brains of Alzheimer’s Disease patients as well as many rodent model systems including those modeling mutations in preseinilin 1 (PSEN1). The aim of our study was to characterize mitochondrial function and number in fibroblasts from AD patients with PSEN1 mutations. Methods We used biochemical assays, metabolic profiling and fluorescent labeling to assess mitochondrial number and function in fibroblasts from three AD patients compared to fibroblasts form three controls. Results The mutant AD fibroblasts showed increased AB42 relative to controls. Reductions in ATP as well as basal and maximal mitochondrial respiration were also observed in these fibroblasts as was impaired spare mitochondrial respiratory capacity. Fluorescent staining and expression of genes encoding electron transport chain enzymes showed diminished mitochondrial content in the AD fibroblasts. Conclusions This study demonstrates that mitochondrial dysfunction is observable in AD fibroblasts and provides evidence that this model system could be useful as a tool to screen disease-modifying compounds.

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“…This system is being used as a standard procedure for all PET imaging in Japan. More than 60% of participants in 28 clinical sites were scanned by FDG-PET, and an in-depth analysis of the multicenter data has started [68][69][70]. Amyloid PET imaging using Pittsburgh Compound B ( 11 C-PiB) was conducted in w15 sites; whereas two sites performed PET studies using 11 C-BF-227.…”

Section: Japanese Adnimentioning

confidence: 99%

The Worldwide Alzheimer's Disease Neuroimaging Initiative: An update

Hendrix

Finger²,

Weiner

et al. 2015

Alzheimer's & Dementia

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The Alzheimer's Disease Neuroimaging Initiative (ADNI), launched in 2004, has worked to accelerate drug development by validating imaging and blood/cerebrospinal fluid biomarkers for Alzheimer's disease clinical treatment trials. ADNI is a naturalistic (nontreatment) multisite longitudinal study. A true public-private partnership, the initiative has set a new standard for data sharing without embargo and for the use of biomarkers in dementia research. The ADNI effort in North America is not the only such effort in the world. The Alzheimer's Association recognized these global efforts and formed Worldwide ADNI (WW-ADNI). By creating a platform for international collaboration and cooperation, WW-ADNI's goals are to harmonize projects and results across geographical regions and to facilitate data management and availability to investigators around the world. WW-ADNI projects include those based in North America, Europe, Japan, Australia, Korea, and Argentina.

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Visual-Statistical Interpretation of 18F-FDG-PET Images for Characteristic Alzheimer Patterns in a Multicenter Study: Inter-Rater Concordance and Relationship to Automated Quantitative Evaluation

Abstract: EBM 2 ABSTRACT BACKGROUND AND PURPOSE:The role of 18 F-FDG-PET in the diagnosis of Alzheimer disease is increasing and should be validated. The

Cited by 42 publications

References 17 publications

Treadmill Exercise Exerts Neuroprotection and Regulates Microglial Polarization and Oxidative Stress in a Streptozotocin-Induced Rat Model of Sporadic Alzheimer’s Disease

Treadmill Exercise Exerts Neuroprotection and Regulates Microglial Polarization and Oxidative Stress in a Streptozotocin-Induced Rat Model of Sporadic Alzheimer’s Disease

Alterations in mitochondrial number and function in Alzheimer’s disease fibroblasts

The Worldwide Alzheimer's Disease Neuroimaging Initiative: An update

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