Differential Regional Cerebral Uptake of &lt;sup&gt;18&lt;/sup&gt;F-Fluoro-2-Deoxy-&lt;i&gt;D&lt;/i&gt;-Glucose in Alzheimer’s Disease and Frontotemporal Dementia at Initial Diagnosis

Santens, Patrick; Bleecker, Jan De; Goethals, Patrick; Strijckmans, Karel; Lemahieu, Ignace; Slegers, Guido; Dierckx, Rudi; Reuck, Jacques De

doi:10.1159/000052084

Cited by 40 publications

(25 citation statements)

References 32 publications

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“…In a comparison between the patients groups, more altered within-lobe frontal and temporal connections were found in FTLD, in line with a more pronounced hypometabolism in this clinical entity. 35,36 Intriguing results were obtained by analyses of between-lobe connections. Whereas the number of abnormal frontoparietal and frontotemporal connections did not differ between AD and FTLD, significantly more abnormal parietotemporal connections were found in AD.…”

Section: Discussionmentioning

confidence: 89%

Metabolic connectivity for differential diagnosis of dementing disorders

Titov

Diehl‐Schmid

Shi

et al. 2016

J Cereb Blood Flow Metab

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Presently, visual and quantitative approaches for image-supported diagnosis of dementing disorders rely on regional intensity rather than on connectivity measurements. Here, we test metabolic connectivity for differentiation between Alzheimer's disease and frontotemporal lobar degeneration. Positron emission tomography with 18F-fluorodeoxyglucose was conducted in 47 patients with mild Alzheimer's disease, 52 patients with mild frontotemporal lobar degeneration, and 45 healthy elderly subjects. Sparse inverse covariance estimation and selection were used to identify patterns of metabolic, inter-subject covariance on the basis of 60 regional values. Relative to healthy subjects, significantly more pathological within-lobe connections were found in the parietal lobe of patients with Alzheimer's disease, and in the frontal and temporal lobes of subjects with frontotemporal lobar degeneration. Relative to the frontotemporal lobar degeneration group, more pathological connections between the parietal and temporal lobe were found in the Alzheimer's disease group. The obtained connectivity patterns differentiated between two patients groups with an overall accuracy of 83%. Linear discriminant analysis and univariate methods provided an accuracy of 74% and 69%, respectively. There are characteristic patterns of abnormal metabolic connectivity in mild Alzheimer's disease and frontotemporal lobar degeneration. Such patterns can be utilized for single-subject analyses and might be more accurate in the differential diagnosis of dementing disorders than traditional intensity-based analyses.

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Section: Discussionmentioning

confidence: 89%

Metabolic connectivity for differential diagnosis of dementing disorders

Titov

Diehl‐Schmid

Shi

et al. 2016

J Cereb Blood Flow Metab

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“…Increasing evidence highlights a connection between AD and mitochondrial dysfunction together with a deregulation of energy metabolism and oxidative stress (8). Various reports have demonstrated markedly reduced levels of mitochondrial proteins and activities (9 -11), decreased glucose turnover (12,13), increased mitochondrial DNA mutations (14 -16), and increased lipid peroxidation (17)(18)(19) in AD brains.…”

Section: Alzheimer Disease (Ad)mentioning

confidence: 99%

Proteomic and Functional Analyses Reveal a Mitochondrial Dysfunction in P301L Tau Transgenic Mice

David

Hauptmann

Scherping

et al. 2005

Journal of Biological Chemistry

389

311

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Transgenic mice overexpressing the P301L mutant human tau protein exhibit an accumulation of hyperphosphorylated tau and develop neurofibrillary tangles. The consequences of tau pathology were investigated here by proteomics followed by functional analysis. Mainly metabolism-related proteins including mitochondrial respiratory chain complex components, antioxidant enzymes, and synaptic proteins were identified as modified in the proteome pattern of P301L tau mice. Significantly, the reduction in mitochondrial complex V levels in the P301L tau mice revealed using proteomics was also confirmed as decreased in human P301L FTDP-17 (frontotemporal dementia with parkinsonism linked to chromosome 17) brains. Functional analysis demonstrated a mitochondrial dysfunction in P301L tau mice together with reduced NADH-ubiquinone oxidoreductase activity and, with age, impaired mitochondrial respiration and ATP synthesis. Mitochondrial dysfunction was associated with higher levels of reactive oxygen species in aged transgenic mice. Increased tau pathology as in aged homozygous P301L tau mice revealed modified lipid peroxidation levels and the upregulation of antioxidant enzymes in response to oxidative stress. Furthermore, P301L tau mitochondria displayed increased vulnerability toward ␤-amyloid (A␤) peptide insult, suggesting a synergistic action of tau and A␤ pathology on the mitochondria. Taken together, we conclude that tau pathology involves a mitochondrial and oxidative stress disorder possibly distinct from that caused by A␤. Alzheimer disease (AD)1 is characterized by two major histopathological hallmarks, extracellular plaques of fibrillar ␤-amyloid (A␤) peptides and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein (1, 2). Mutations in tau have been identified in a related neurodegenerative disorder called frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) with NFT formation in the absence of plaque formation (3-5). Transgenic mice overexpressing the P301L mutant human tau protein were created to model tauopathies in vivo (6, 7). These mice show an accumulation of hyperphosphorylated tau and NFT formation similar to those in FTDP-17 and AD.Little is known about the distinct intracellular mechanisms underlying the consequences of tau pathology. This insight could help us to understand the selective vulnerability of cells with tau pathology and thereby the pathogenesis of AD. Increasing evidence highlights a connection between AD and mitochondrial dysfunction together with a deregulation of energy metabolism and oxidative stress (8). Various reports have demonstrated markedly reduced levels of mitochondrial proteins and activities (9 -11), decreased glucose turnover (12, 13), increased mitochondrial DNA mutations (14 -16), and increased lipid peroxidation (17-19) in AD brains.To examine the contribution of tau to these neurodegenerative processes, we carried out a proteomic analysis of our P301L tau transgenic mice. To zoom in on proteins relevant to the p...

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“…Regional brain metabolism is a sensitive indicator of Alzheimer's dementia (AD) and neurodegenerative diseases in general. 31 Considerable data exists that supports the idea that the pattern of metabolism and perfusion abnormalities in AD is quite different from frontal lobe dementia, which is characterized by reduced frontal lobe metabolism and perfusion. 31 In AD, there is temporoparietal hypometabolism.…”

Section: Pet In Neurologymentioning

confidence: 99%

“…31 Considerable data exists that supports the idea that the pattern of metabolism and perfusion abnormalities in AD is quite different from frontal lobe dementia, which is characterized by reduced frontal lobe metabolism and perfusion. 31 In AD, there is temporoparietal hypometabolism. 32 Dementia with Lewy Bodies is also clinically different than AD, displaying temporoparietal hypometabolism along with abnormalities in the visual association cortex of the occipital lobe.…”

Section: Pet In Neurologymentioning

confidence: 99%

PET in Halifax

Chung¹,

Zoost²,

Burrell³

2011

DMJ

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With the recent installation of a PET-CT scanner in Halifax, local clinicians may now take advantage of PET's various applications in the field of oncology, where it has become a standard of care. PET also plays a role in the areas of cardiology and neurology although it has not yet been approved for these uses in Nova Scotia. This article describes the basic principles of PET and radiopharmaceuticals as well as PET's increasing role in the management of patients in the areas of oncology, neurology and cardiology. PET shows significant promise in these areas and clinicians should be familiar with its many applications.

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Differential Regional Cerebral Uptake of <sup>18</sup>F-Fluoro-2-Deoxy-<i>D</i>-Glucose in Alzheimer’s Disease and Frontotemporal Dementia at Initial Diagnosis

Cited by 40 publications

References 32 publications

Metabolic connectivity for differential diagnosis of dementing disorders

Metabolic connectivity for differential diagnosis of dementing disorders

Proteomic and Functional Analyses Reveal a Mitochondrial Dysfunction in P301L Tau Transgenic Mice

PET in Halifax

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