Contrasting metabolic impairment in frontotemporal degeneration and early onset Alzheimer's disease

Ibach, Bernd; Poljansky, Stefan; Marienhagen, Jörg; Sommer, Monika; Männer, Peter; Hajak, Göran

doi:10.1016/j.neuroimage.2004.06.041

Cited by 63 publications

(26 citation statements)

References 35 publications

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“…1984; de la Torre, 1999;Matsuda, 2001;Matsuda et al, 2002), and glucose metabolism is reduced in both preclinical and clinical AD (de Leon et al, 1983a,b;Cutler et al, 1985;Rapoport et al, 1991;Meier-Ruge et al, 1994;Reiman et al, 1996;Rapoport, 1999;Small et al, 2000;De Santis et al, 2001;Ibach et al, 2004;Mosconi et al, 2004;Mosconi, 2005), suggesting that impaired energy metabolism may be an early pathological event in SAD. Moreover, cardiovascular diseases appear to increase the risk of AD (Breteler, 2000;Shi et al, 2000;de la Torre, 2004) and the incidence of cerebrovascular atherosclerosis is higher in AD (Roher et al, 2003;Kalback et al, 2004).…”

Section: Potential Mechanisms Underlying the Persistent Bace1 Increasementioning

confidence: 99%

Energy Inhibition Elevates β-Secretase Levels and Activity and Is Potentially Amyloidogenic in APP Transgenic Mice: Possible Early Events in Alzheimer's Disease Pathogenesis

Velliquette¹,

O’Connor²,

Vassar³

2005

J. Neurosci.

236

186

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␤-Secretase [␤-site amyloid precursor protein-cleaving enzyme 1 (BACE1)] is the key rate-limiting enzyme for the production of the ␤-amyloid (A␤) peptide involved in the pathogenesis of Alzheimer's disease (AD). BACE1 levels and activity are increased in AD brain and are likely to drive A␤ overproduction, but the cause of BACE1 elevation in AD is unknown. Interestingly, cerebral glucose metabolism and blood flow are both reduced in preclinical AD, suggesting that impaired energy production may be an early pathologic event in AD. To determine whether reduced energy metabolism would cause BACE1 elevation, we used pharmacological agents (insulin, 2-deoxyglucose, 3-nitropropionic acid, and kainic acid) to induce acute energy inhibition in C57/B6 wild-type and amyloid precursor protein (APP) transgenic (Tg2576) mice. Four hours after treatment, we observed that reduced energy production caused a ϳ150% increase of cerebral BACE1 levels compared with control. Although this was a modest increase, the effect was long-lasting, because levels of the BACE1 enzyme remained elevated for at least 7 d after a single dose of energy inhibitor. In Tg2576 mice, levels of the BACE1-cleaved APP ectodomain APPs␤ were also elevated and paralleled the BACE1 increase in both relative amount and duration. Importantly, cerebral A␤40 levels in Tg2576 were increased to ϳ200% of control at 7 d after injection, demonstrating that energy inhibition was potentially amyloidogenic. These results support the hypothesis that impaired energy production in the brain may drive AD pathogenesis by elevating BACE1 levels and activity, which, in turn, lead to A␤ overproduction. This process may represent one of the earliest pathogenic events in AD.

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Section: Potential Mechanisms Underlying the Persistent Bace1 Increasementioning

confidence: 99%

Energy Inhibition Elevates β-Secretase Levels and Activity and Is Potentially Amyloidogenic in APP Transgenic Mice: Possible Early Events in Alzheimer's Disease Pathogenesis

Velliquette¹,

O’Connor²,

Vassar³

2005

J. Neurosci.

236

186

View full text Add to dashboard Cite

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“…For example, compared to historical normal controls, patients with AD show an abnormally low uptake in the posterior cingulate, precuneus, medial temporal lobe, temporoparietal regions and frontal cortex, whereas patients with FTD show an early and more severe frontal and anterior/mesial temporal hypometabolism pattern that is often asymmetrical. [12][13][14][15] In the United States, this led to the approval in 2004 of FDG-PET as a routine examination tool for the differential diagnosis of AD from FTD (Expert Panel of the National Institute of Aging/Centers for Medicare and Medicaid Services). Dementia with Lewy Bodies patterns closely mirror those observed in AD with added reduction in the occipital lobe, particularly in the primary visual cortex.…”

Section: Introductionmentioning

confidence: 99%

The Value of PET in Mild Cognitive Impairment, Typical and Atypical/Unclear Dementias: A Retrospective Memory Clinic Study

Laforce

Buteau

Paquet

et al. 2010

Am J Alzheimers Dis Other Demen

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This retrospective study examined the role of [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) in the diagnosis of atypical/unclear dementias in a memory clinic setting. A total of 94 patients with a diagnosis of mild cognitive impairment (MCI) or dementia, who had a PET study within 2 months of their diagnosis, were reevaluated at 5 and 18 months. Results showed that PET was associated with a change in diagnosis in 29% of patients and a 64% increase in the use of cholinesterase inhibitors (ChEIs). PET significantly lowered the number of atypical/unclear diagnoses from 39.4% to 16% and nearly 30% of these were found to have a typical Alzheimer's disease (AD) pattern of hypometabolism. In conclusion, the addition of PET to the investigation of atypical/unclear cases of dementia helped generating a more accurate diagnosis and initiating earlier treatment. PET was of limited contribution to typical AD and frontotemporal dementia (FTD) cases. This study provides guiding evidence about the true value of PET imaging in the day-to-day challenge of dementia diagnosis.

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“…Several PET studies in AD, FTLD and FTD have been performed [18][19][20] . However, to our knowledge, there are -with one exception [9] -no studies in SD that take advantage of PET in cross-sectional or longitudinal studies, although using abnormalities of metabolic activity as a marker, this technique can identify neurodegenerative processes before atrophy becomes apparent on structural imaging [21] .…”

Section: Introductionmentioning

confidence: 99%

“…The aim of this study was to determine the progression of changes in cerebral glucose metabolism in SD in a follow-up study using 18 F-fluoro-2-desoxy-D -glucose positron emission tomography scanning ( 18 F-FDG-PET). We investigated reductions in regional cerebral glucose metabolism of 8 patients with SD compared to cognitively healthy control (HC) subjects at baseline and in average 15 months later and sought to identify specific brain regions showing maximal decline.…”

Section: Introductionmentioning

confidence: 99%

Longitudinal Changes of Cerebral Glucose Metabolism in Semantic Dementia

Diehl‐Schmid

Grimmer²,

Drzezga³

et al. 2006

Dement Geriatr Cogn Disord

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Background: Semantic dementia (SD). Objective: To identify the pattern of decline of cerebral glucose metabolism in SD using cerebral ¹⁸F-fluoro-2-desoxy-D-glucose positron emission tomography scanning (¹⁸F-FDG-PET). Methods: Eight patients with SD underwent ¹⁸F-FDG-PET at baseline and at re-examination in average 15 months later. Results: Compared with healthy control subjects, patients with SD showed a significant asymmetrical (left > right) hypometabolism of the temporal lobes, particularly of the anterior poles, at baseline. At follow-up, we observed a deterioration of cognitive abilities. However, in addition to the temporal lobes no other cortical or subcortical region showed a significant reduction of glucose metabolism except the anterior cingulate cortex (pcorr < 0.05). Conclusion: Subtle functional changes suffice to produce significant neuropsycho- logical deterioration.

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Contrasting metabolic impairment in frontotemporal degeneration and early onset Alzheimer's disease

Cited by 63 publications

References 35 publications

Energy Inhibition Elevates β-Secretase Levels and Activity and Is Potentially Amyloidogenic in APP Transgenic Mice: Possible Early Events in Alzheimer's Disease Pathogenesis

Energy Inhibition Elevates β-Secretase Levels and Activity and Is Potentially Amyloidogenic in APP Transgenic Mice: Possible Early Events in Alzheimer's Disease Pathogenesis

The Value of PET in Mild Cognitive Impairment, Typical and Atypical/Unclear Dementias: A Retrospective Memory Clinic Study

Longitudinal Changes of Cerebral Glucose Metabolism in Semantic Dementia

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