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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Mecca, Adam P. McDonald, Julia W. Michalak, Hannah R. Godek, Tyler A. Harris, Joanna E. Pugh, Erika A. Kemp, Emily C. Chen, Ming-Kai Salardini, Arash Nabulsi, Nabeel B. Lim, Keunpoong Huang, Yiyun Carson, Richard E. Strittmatter, Stephen M. van Dyck, Christopher H. |
| Abstract | Background Metabotropic glutamate subtype 5 receptors (mGluR5) modulate synaptic transmission and may constitute an important therapeutic target in Alzheimer’s disease (AD) by mediating the synaptotoxic action of amyloid-β oligomers. We utilized the positron emission tomography (PET) radioligand [18F]FPEB to investigate mGluR5 binding in early AD. Methods Sixteen individuals with amnestic mild cognitive impairment (MCI) due to AD or mild AD dementia who were positive for brain amyloid were compared to 15 cognitively normal (CN) participants who were negative for brain amyloid. Diagnostic groups were well balanced for age, sex, and education. Dynamic PET scans were acquired for 60 min, starting at 60 min after the initial administration of up to 185 MBq of [18F]FPEB using a bolus-plus-constant-infusion method (Kbol = 190 min). Equilibrium modeling with a cerebellum reference region was used to estimate [18F]FPEB binding (BPND) to mGluR5. Analyses were performed with and without corrections for gray matter atrophy and partial volume effects. Results Linear mixed model analysis demonstrated a significant effect of group (p = 0.011) and the group × region interaction (p = 0.0049) on BPND. Post hoc comparisons revealed a significant reduction (43%) in mGluR5 binding in the hippocampus of AD (BPND = 0.76 ± 0.41) compared to CN (BPND = 1.34 ± 0.58, p = 0.003, unpaired t test) participants, and a nonsignificant trend for a reduction in a composite association cortical region in AD (BPND = 1.57 ± 0.25) compared to CN (BPND = 1.86 ± 0.63, p = 0.093) participants. Exploratory analyses suggested additional mGluR5 reductions in the entorhinal cortex and parahippocampal gyrus in the AD group. In the overall sample, hippocampal mGluR5 binding was associated with episodic memory scores and global function. Conclusions [18F]FPEB-PET revealed reductions in hippocampal mGluR5 binding in early AD. Quantification of mGluR5 binding in AD may expand our understanding of AD pathogenesis and accelerate the development of novel biomarkers and treatments. |
| Related Links | https://alzres.biomedcentral.com/counter/pdf/10.1186/s13195-020-0582-0.pdf |
| Ending Page | 10 |
| Page Count | 10 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 17589193 |
| DOI | 10.1186/s13195-020-0582-0 |
| Journal | Alzheimer's Research & Therapy |
| Issue Number | 1 |
| Volume Number | 12 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2020-01-18 |
| Access Restriction | Open |
| Subject Keyword | Neurosciences Neurology Geriatrics Gerontology Geriatric Psychiatry mGluR5 Glutamate receptor Alzheimer’s disease [18F]FPEB PET Geriatrics/Gerontology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neurology Neurology (clinical) Cognitive Neuroscience |
| Journal Impact Factor | 8/2023 |
| 5-Year Journal Impact Factor | 8.3/2023 |
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