Tags

Type your tag names separated by a space and hit enter

In vivo molecular neuroimaging of glucose utilization and its association with fibrillar amyloid-β load in aged APPPS1-21 mice.
Alzheimers Res Ther. 2015 Dec 15; 7(1):76.AR

Abstract

INTRODUCTION

Radioligand imaging is a powerful in vivo method to assess the molecular basis of Alzheimer's Disease. We therefore aimed to visualize the pathological deposition of fibrillar amyloid-β and neuronal dysfunction in aged double transgenic mice.

METHODS

Using non-invasive positron emission tomography (PET) we assessed brain glucose utilization with [(18)F]FDG and fibrillar amyloidosis with [(11)C]PiB and [(18)F]AV45 in 12 month old APPPS1-21 (n = 10) mice and their age-matched wild-type controls (n = 15). PET scans were analyzed with statistical parametric mapping (SPM) to detect significant differences in tracer uptake between genotypes. After imaging, mice were sacrificed and ex vivo measures of amyloid-β burden with immunohistochemistry as well as glucose utilization with [(14)C]-2DG autoradiography were obtained as gold standards.

RESULTS

Voxel-wise SPM analysis revealed significantly decreased [(18)F]FDG uptake in aged APPPS1-21 mice in comparison to WT with the thalamus (96.96 %, maxT = 3.35) and striatum (61.21 %, maxT = 3.29) demonstrating the most widespread reductions at the threshold of p < 0.01. [(11)C]PiB binding was significantly increased in APPPS1-21 mice, most notably in the hippocampus (87.84 %, maxT = 7.15) and cortex (69.08 %, maxT = 7.95), as detected by SPM voxel-wise analysis at the threshold of p < 0.01. Using the same threshold [(18)F]AV45 uptake was comparably lower with less significant differences. Compared to their respective ex vivo equivalents [(18)F]FDG demonstrated significant positive correlation to [(14)C]2-DG autoradiography (r = 0.67, p <0.0001) while [(11)C]PiB and [(18)F]AV45 binding did not correlate to ex vivo immunohistochemistry for amyloid-β (r = 0.25, p = 0.07 and r = 0.17, p = 0.26 respectively). Lastly no correlation was observed between regions of high amyloid burden and those with decreased glucose utilization (r = 0.001, p = 0.99).

CONCLUSIONS

Our findings support that fibrillar amyloid-β deposition and reduced glucose utilization can be visualized and quantified with in vivo μPET imaging in aged APPPS1-21 mice. Therefore, the combined use of [(18)F]FDG and amyloid μPET imaging can shed light on the underlying relationship between fibrillar amyloid-β pathology and neuronal dysfunction.

Authors+Show Affiliations

Molecular Imaging Center Antwerp, University of Antwerp, Campus Drie Eiken - UC, Universiteitsplein 1, 2610, Wilrijk, Antwerp, Belgium. Ann-marie.waldron@uantwerpen.be.Neuroscience Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium. Cwintmol@its.jnj.com.Neuroscience Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium. Abottelb@its.jnj.com.Neuroscience Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium. Jkelley3@its.jnj.com.Neuroscience Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium. mschmid4@its.jnj.com.Molecular Imaging Center Antwerp, University of Antwerp, Campus Drie Eiken - UC, Universiteitsplein 1, 2610, Wilrijk, Antwerp, Belgium. Sigrid.Stroobants@uza.be. Nuclear Medicine Department, University Hospital Antwerp, Antwerp, Belgium. Sigrid.Stroobants@uza.be.Neuroscience Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium. Xlangloi@its.jnj.com.Molecular Imaging Center Antwerp, University of Antwerp, Campus Drie Eiken - UC, Universiteitsplein 1, 2610, Wilrijk, Antwerp, Belgium. steven.staelens@uantwerpen.be.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26666747

Citation

Waldron, Ann-Marie, et al. "In Vivo Molecular Neuroimaging of Glucose Utilization and Its Association With Fibrillar Amyloid-β Load in Aged APPPS1-21 Mice." Alzheimer's Research & Therapy, vol. 7, no. 1, 2015, p. 76.
Waldron AM, Wintmolders C, Bottelbergs A, et al. In vivo molecular neuroimaging of glucose utilization and its association with fibrillar amyloid-β load in aged APPPS1-21 mice. Alzheimers Res Ther. 2015;7(1):76.
Waldron, A. M., Wintmolders, C., Bottelbergs, A., Kelley, J. B., Schmidt, M. E., Stroobants, S., Langlois, X., & Staelens, S. (2015). In vivo molecular neuroimaging of glucose utilization and its association with fibrillar amyloid-β load in aged APPPS1-21 mice. Alzheimer's Research & Therapy, 7(1), 76. https://doi.org/10.1186/s13195-015-0158-6
Waldron AM, et al. In Vivo Molecular Neuroimaging of Glucose Utilization and Its Association With Fibrillar Amyloid-β Load in Aged APPPS1-21 Mice. Alzheimers Res Ther. 2015 Dec 15;7(1):76. PubMed PMID: 26666747.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vivo molecular neuroimaging of glucose utilization and its association with fibrillar amyloid-β load in aged APPPS1-21 mice. AU - Waldron,Ann-Marie, AU - Wintmolders,Cindy, AU - Bottelbergs,Astrid, AU - Kelley,Jonathan B, AU - Schmidt,Mark E, AU - Stroobants,Sigrid, AU - Langlois,Xavier, AU - Staelens,Steven, Y1 - 2015/12/15/ PY - 2015/07/22/received PY - 2015/10/21/accepted PY - 2015/12/16/entrez PY - 2015/12/17/pubmed PY - 2016/5/4/medline SP - 76 EP - 76 JF - Alzheimer's research & therapy JO - Alzheimers Res Ther VL - 7 IS - 1 N2 - INTRODUCTION: Radioligand imaging is a powerful in vivo method to assess the molecular basis of Alzheimer's Disease. We therefore aimed to visualize the pathological deposition of fibrillar amyloid-β and neuronal dysfunction in aged double transgenic mice. METHODS: Using non-invasive positron emission tomography (PET) we assessed brain glucose utilization with [(18)F]FDG and fibrillar amyloidosis with [(11)C]PiB and [(18)F]AV45 in 12 month old APPPS1-21 (n = 10) mice and their age-matched wild-type controls (n = 15). PET scans were analyzed with statistical parametric mapping (SPM) to detect significant differences in tracer uptake between genotypes. After imaging, mice were sacrificed and ex vivo measures of amyloid-β burden with immunohistochemistry as well as glucose utilization with [(14)C]-2DG autoradiography were obtained as gold standards. RESULTS: Voxel-wise SPM analysis revealed significantly decreased [(18)F]FDG uptake in aged APPPS1-21 mice in comparison to WT with the thalamus (96.96 %, maxT = 3.35) and striatum (61.21 %, maxT = 3.29) demonstrating the most widespread reductions at the threshold of p < 0.01. [(11)C]PiB binding was significantly increased in APPPS1-21 mice, most notably in the hippocampus (87.84 %, maxT = 7.15) and cortex (69.08 %, maxT = 7.95), as detected by SPM voxel-wise analysis at the threshold of p < 0.01. Using the same threshold [(18)F]AV45 uptake was comparably lower with less significant differences. Compared to their respective ex vivo equivalents [(18)F]FDG demonstrated significant positive correlation to [(14)C]2-DG autoradiography (r = 0.67, p <0.0001) while [(11)C]PiB and [(18)F]AV45 binding did not correlate to ex vivo immunohistochemistry for amyloid-β (r = 0.25, p = 0.07 and r = 0.17, p = 0.26 respectively). Lastly no correlation was observed between regions of high amyloid burden and those with decreased glucose utilization (r = 0.001, p = 0.99). CONCLUSIONS: Our findings support that fibrillar amyloid-β deposition and reduced glucose utilization can be visualized and quantified with in vivo μPET imaging in aged APPPS1-21 mice. Therefore, the combined use of [(18)F]FDG and amyloid μPET imaging can shed light on the underlying relationship between fibrillar amyloid-β pathology and neuronal dysfunction. SN - 1758-9193 UR - https://www.unboundmedicine.com/medline/citation/26666747/In_vivo_molecular_neuroimaging_of_glucose_utilization_and_its_association_with_fibrillar_amyloid_β_load_in_aged_APPPS1_21_mice_ L2 - https://alzres.biomedcentral.com/articles/10.1186/s13195-015-0158-6 DB - PRIME DP - Unbound Medicine ER -