Insight into the Molecular Imaging of Alzheimer’s Disease

Arora, Abishek; Bhagat, Neeta

doi:10.1155/2016/7462014

Cited by 16 publications

(9 citation statements)

References 168 publications

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“…In general, measurement of the effect of CR by [ 18 F]FDG PET-CT opens the possibility to monitor CR-induced neuroprotection using a noninvasive method and, in particular, in a longitudinal manner. In addition to [ 18 F]FDG-PET/CT, 1H-MRS represents another in vivo technique which allows for the characterization of metabolic changes in AD brains [ 43 , 44 ]. NAA, as a representative metabolite of neuronal integrity, is found to be reduced in AD, indicating neuronal malfunction either due to diminished neuronal density, neuronal cell loss, or partially reversible neuronal dysfunction [ 45 ], and correlates with disease progression [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Long-Term Caloric Restriction Attenuates β-Amyloid Neuropathology and Is Accompanied by Autophagy in APPswe/PS1delta9 Mice

et al. 2021

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Caloric restriction (CR) slows the aging process, extends lifespan, and exerts neuroprotective effects. It is widely accepted that CR attenuates β-amyloid (Aβ) neuropathology in models of Alzheimer’s disease (AD) by so-far unknown mechanisms. One promising process induced by CR is autophagy, which is known to degrade aggregated proteins such as amyloids. In addition, autophagy positively regulates glucose uptake and may improve cerebral hypometabolism—a hallmark of AD—and, consequently, neural activity. To evaluate this hypothesis, APPswe/PS1delta9 (tg) mice and their littermates (wild-type, wt) underwent CR for either 16 or 68 weeks. Whereas short-term CR for 16 weeks revealed no noteworthy changes of AD phenotype in tg mice, long-term CR for 68 weeks showed beneficial effects. Thus, cerebral glucose metabolism and neuronal integrity were markedly increased upon 68 weeks CR in tg mice, indicated by an elevated hippocampal fluorodeoxyglucose [18F] ([18F]FDG) uptake and increased N-acetylaspartate-to-creatine ratio using positron emission tomography/computer tomography (PET/CT) imaging and magnet resonance spectroscopy (MRS). Improved neuronal activity and integrity resulted in a better cognitive performance within the Morris Water Maze. Moreover, CR for 68 weeks caused a significant increase of LC3BII and p62 protein expression, showing enhanced autophagy. Additionally, a significant decrease of Aβ plaques in tg mice in the hippocampus was observed, accompanied by reduced microgliosis as indicated by significantly decreased numbers of iba1-positive cells. In summary, long-term CR revealed an overall neuroprotective effect in tg mice. Further, this study shows, for the first time, that CR-induced autophagy in tg mice accompanies the observed attenuation of Aβ pathology.

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Section: Discussionmentioning

confidence: 99%

Long-Term Caloric Restriction Attenuates β-Amyloid Neuropathology and Is Accompanied by Autophagy in APPswe/PS1delta9 Mice

et al. 2021

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“…Brain morphometry based on high resolution MRI is considered a proxy of neuronal loss in humans ( Bobinski et al, 2000 ). Proton magnetic resonance spectroscopy ( 1 H-MRS) is an in-vivo technique to analyze neuronal functional viability in transgenic animal models ( Mlynárik et al, 2012 ) and human studies ( Arora and Bhagat, 2016 ). Each observable metabolite can potentially serve as a marker being representative for pathological processes at a molecular or cellular level.…”

Section: Introductionmentioning

confidence: 99%

APPswe/PS1dE9 mice with cortical amyloid pathology show a reduced NAA/Cr ratio without apparent brain atrophy: A MRS and MRI study

Kuhla

Rühlmann

Lindner

et al. 2017

NeuroImage: Clinical

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Transgenic animal models of Aβ pathology provide mechanistic insight into some aspects of Alzheimer disease (AD) pathology related to Aβ accumulation. Quantitative neuroimaging is a possible aid to improve translation of mechanistic findings in transgenic models to human end phenotypes of brain morphology or function. Therefore, we combined MRI-based morphometry, MRS-based NAA-assessment and quantitative histology of neurons and amyloid plaque load in the APPswe/PS1dE9 mouse model to determine the interrelationship between morphological changes, changes in neuron numbers and amyloid plaque load with reductions of NAA levels as marker of neuronal functional viability. The APPswe/PS1dE9 mouse showed an increase of Aβ plaques, loss of neurons and an impairment of NAA/Cr ratio, which however was not accompanied with brain atrophy. As brain atrophy is one main characteristic in human AD, conclusions from murine to human AD pathology should be drawn with caution.

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“…Here, a pre-clinical study reported that mice carrying the human APOE 4 isoform (hApoE4-TR) showed decreased [ 18 F]FDG uptake [18]. Complementary to [ 18 F] FDG-PET/CT, proton magnetic resonance spectroscopy ( 1 H-MRS) allows characterization of neurochemical alterations in AD brains [19]. N-Acetylaspartate (NAA) is considered to reflect neuronal mitochondrial function [20,21].…”

Section: Introductionmentioning

confidence: 99%

Longitudinal [18F]FDG-PET/CT analysis of the glucose metabolism in ApoE-deficient mice

et al. 2020

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Background Strong line of evidence suggests that the increased risk to develop AD may at least be partly mediated by cholesterol metabolism. A key regulator of cholesterol transport is the Apolipoprotein E4 (ApoE4), which plays a fundamental role in neuronal maintenance and repair. Impaired function of ApoE4 may contribute to altered cerebral metabolism leading to higher susceptibility to neurodegeneration. Methods To determine a possible link between ApoE function and alterations in AD in the brain of Apolipoprotein E-deficient mice (ApoE−/−) in a longitudinal manner metabolic and neurochemical parameters were analyzed. Cortical metabolism was measured by 2-deoxy-2-[18F]fluoroglucose ([18F]FDG)-PET/CT and proton magnetic resonance spectroscopy (1H-MRS) served to record neurochemical status. Results By using [18F]FDG-PET/CT, we showed that brain metabolism declined significantly stronger with age in ApoE−/− versus wild type (wt) mice. This difference was particularly evident at the age of 41 weeks in almost each analyzed brain region. In contrast, the 1H-MRS-measured N-acetylaspartate to creatine ratio, a marker of neuronal viability, did not decline with age and did not differ between ApoE−/− and wt mice. Conclusion In summary, this longitudinal in vivo study shows for the first time that ApoE−/− mice depict cerebral hypometabolism without neurochemical alterations.

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Insight into the Molecular Imaging of Alzheimer’s Disease

Cited by 16 publications

References 168 publications

Long-Term Caloric Restriction Attenuates β-Amyloid Neuropathology and Is Accompanied by Autophagy in APPswe/PS1delta9 Mice

Long-Term Caloric Restriction Attenuates β-Amyloid Neuropathology and Is Accompanied by Autophagy in APPswe/PS1delta9 Mice

APPswe/PS1dE9 mice with cortical amyloid pathology show a reduced NAA/Cr ratio without apparent brain atrophy: A MRS and MRI study

Longitudinal [18F]FDG-PET/CT analysis of the glucose metabolism in ApoE-deficient mice

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