In vivo evaluation of amyloid deposition and brain glucose metabolism of 5XFAD mice using positron emission tomography

Rojas, Santiago; Herance, José Raúl; Gispert, Juan Domingo; Abad, Sergio; Torrent, Èlia; Jiménez, Xavier F.; Pareto, Deborah; Perpiñá, Unai; Sarroca, Sara; Rodrı́guez, Elisenda; Ortega‐Aznar, Arantxa; Sanfeliu, Coral

doi:10.1016/j.neurobiolaging.2012.12.027

Cited by 71 publications

(79 citation statements)

References 33 publications

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“…In contrast to these results, a recent study [10] found that brain 18 FDG uptake increased relative to the cerebellum in older 5XFAD mice. A similar analysis in the present study demonstrated no significant difference between the whole brain relative to the cerebellum in 5XFAD and WT mice (Fig.…”

Section: Discussionmentioning

confidence: 69%

“…Nonetheless, some abnormalities seen in human AD are recapitulated in this mouse model. For example, defective glucose uptake [10], impaired mitochondrial energy metabolism and synaptic damage [34, 35] may play a significant role in the progression of AD. As in the later stages of human AD, it is not until later in the 5XFAD disease stage (13 months) that profound 18 FDG uptake changes were observed in the brain using direct SUV measurements.…”

Section: Discussionmentioning

confidence: 99%

“…Under the amyloid cascade hypothesis [6], the presence and aggregation of Aβ leads to events that result in neurotoxicity and neurodegeneration in AD.To further examine the role of Aβ deposition in AD pathogenesis, transgenic mouse models of brain amyloidosis have been developed, based on familial AD (FAD) mutations, that result in brain Aβ accumulation. Similar to human AD, these animals have demonstrated synaptic loss [7], mitochondrial abnormalities [8, 9], activated microglia/neuroinflammation [7, 10] and neuronal loss [7]. It has been postulated that deposition of Aβ and its deleterious effects on neurons may result in decreased glucose metabolism in AD and, thus, the effect of Aβ deposition on brain 18 FDG uptake can be explored using mouse models [11].…”

Section: Introductionmentioning

confidence: 99%

“…Brain glucose metabolism was reported to be elevated in 12-15 month old 5XFAD mice [10]. However, the progression of brain glucose metabolism across the lifespan of this mouse, and potential differences in specific brain regions, have not been examined.…”

Section: Introductionmentioning

confidence: 99%

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Early Detection of Cerebral Glucose Uptake Changes in the 5XFAD Mouse

Macdonald¹,

DeBay²,

Reid³

et al. 2014

CAR

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Brain glucose hypometabolism has been observed in Alzheimer’s disease (AD) patients, and is detected with 18F radiolabelled glucose, using positron emission tomography. A pathological hallmark of AD is deposition of brain β-amyloid plaques that may influence cerebral glucose metabolism. The five times familial AD (5XFAD) mouse is a model of brain amyloidosis exhibiting AD-like phenotypes. This study examines brain β-amyloid plaque deposition and 18FDG uptake, to search for an early biomarker distinguishing 5XFAD from wild-type mice. Thus, brain 18FDG uptake and plaque deposition was studied in these mice at age 2, 5 and 13 months. The 5XFAD mice demonstrated significantly reduced brain 18FDG uptake at 13 months relative to wild-type controls but not in younger mice, despite substantial β-amyloid plaque deposition. However, by comparing the ratio of uptake values for glucose in different regions in the same brain, 5XFAD mice could be distinguished from controls at age 2 months. This method of measuring altered glucose metabolism may represent an early biomarker for the progression of amyloid deposition in the brain. We conclude that brain 18FDG uptake can be a sensitive biomarker for early detection of abnormal metabolism in the 5XFAD mouse when alternative relative uptake values are utilized.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Early Detection of Cerebral Glucose Uptake Changes in the 5XFAD Mouse

Macdonald¹,

DeBay²,

Reid³

et al. 2014

CAR

View full text Add to dashboard Cite

show abstract

“…Thus far, reports using in vivo PET and MRI in transgenic animal models of AD using [ 11 10,11,21,24 . These approaches lack PET quantification or require transient opening of the blood-brain barrier for MRI contrast agents [2][3][4]8,25,26 . Quantifying the β-amyloid burden in small rodents is of paramount interest for the evaluation of new treatment strategies targeting β-amyloid; however, to our knowledge, there have only been a few encouraging reports on β-amyloid imaging using [ 11 C]PIB-PET in transgenic mice that have demonstrated the feasibility of this strategy 10,11,21,24 .…”

Section: Discussionmentioning

confidence: 99%

Longitudinal PET-MRI reveals β-amyloid deposition and rCBF dynamics and connects vascular amyloidosis to quantitative loss of perfusion

Maier

Wehrl

Schmid

et al. 2014

Nat Med

112

110

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The dynamics of β-amyloid deposition and related second-order physiological effects, such as regional cerebral blood flow (rCBF), are key factors for a deeper understanding of Alzheimer's disease (AD). We present longitudinal in vivo data on the dynamics of β-amyloid deposition and the decline of rCBF in two different amyloid precursor protein (APP) transgenic mouse models of AD. Using a multiparametric positron emission tomography and magnetic resonance imaging approach, we demonstrate that in the presence of cerebral β-amyloid angiopathy (CAA), β-amyloid deposition is accompanied by a decline of rCBF. Loss of perfusion correlates with the growth of β-amyloid plaque burden but is not related to the number of CAA-induced microhemorrhages. However, in a mouse model of parenchymal β-amyloidosis and negligible CAA, rCBF is unchanged. Because synaptically driven spontaneous network activity is similar in both transgenic mouse strains, we conclude that the disease-related decline of rCBF is caused by CAA.

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Brain metabolic network covariance and aging in a mouse model of Alzheimer's disease

Chumin,

Burton,

Silvola

et al. 2023

Alzheimer's & Dementia

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INTRODUCTIONAlzheimer's disease (AD), the leading cause of dementia worldwide, represents a human and financial impact for which few effective drugs exist to treat the disease. Advances in molecular imaging have enabled assessment of cerebral glycolytic metabolism, and network modeling of brain region have linked to alterations in metabolic activity to AD stage.METHODSWe performed 18F‐FDG positron emission tomography (PET) imaging in 4‐, 6‐, and 12‐month‐old 5XFAD and littermate controls (WT) of both sexes and analyzed region data via brain metabolic covariance analysis.RESULTSThe 5XFAD model mice showed age‐related changes in glucose uptake relative to WT mice. Analysis of community structure of covariance networks was different across age and sex, with a disruption of metabolic coupling in the 5XFAD model.DISCUSSIONThe current study replicates clinical AD findings and indicates that metabolic network covariance modeling provides a translational tool to assess disease progression in AD models.

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In vivo evaluation of amyloid deposition and brain glucose metabolism of 5XFAD mice using positron emission tomography

Cited by 71 publications

References 33 publications

Early Detection of Cerebral Glucose Uptake Changes in the 5XFAD Mouse

Early Detection of Cerebral Glucose Uptake Changes in the 5XFAD Mouse

Longitudinal PET-MRI reveals β-amyloid deposition and rCBF dynamics and connects vascular amyloidosis to quantitative loss of perfusion

Brain metabolic network covariance and aging in a mouse model of Alzheimer's disease

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