DT‐02–05: <i>In vivo</i> characterization of metabotropic glutamate receptor type five vulnerability in behavioral variant FTD and Alzheimer's disease: An [<sup>11</sup>C]ABP688 PET/ VBM /DBM study
Bibliographic record
Abstract
Behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) are progressive neurodegenerative syndromes characterized by atrophy in frontal, limbic, and temporal brain regions. While glutamatergic projection neurons are highly affected in both diseases, such abnormalities have yet to be systemically characterized, principally due the lack of suitable molecular probes. Using [11C]ABP688, a novel Positron Emission Tomography (PET) radiopharmaceutical for in-vivo quantification of mGluR5, and voxel based/deformation based morphometry (VBM/DBM), we sought to determine the extent of receptor decrements and the overlap between the topography of such declines and atrophy within frontal, limbic, and temporal brain regions. We analyzed a sample of 5 bvFTD and 8 AD subjects who had [C]ABP688/MRI data collected within a two-week period. Diagnosis of bvFTD and AD were issued on the basis of the FTDC criteria, and the NIA-AA criteria, respectively. PET binding potential maps (BPND) were calculated using the cerebellar cortex as a reference region. PET images were subsequently registered to ICBM152 space nonlinearly. For VBM, T1 MRIs were registered to ICBM152 space nonlinearly, and segmented into gray matter (GM), white matter (GM), and cerebrospinal fluid (CSF). GM maps were then blurred with a 10mm Gaussian kernel. For DBM, the magnitude of each vector of the Jacobian deformation field was computed. Voxel-based group differences were obtained by comparing bvFTD and AD using RMINC. No significant between group differences were found in terms of age, gender, handedness, educational attainment and MMSE (p < 0.05). Relative to AD, bvFTD was associated with greater decrements in mGluR5, with maxima in orbitofrontal cortex, insula, superior temporal gyrus, frontal opercula, and anterior temporal lobe. Structural changes were likewise greater in bvFTD, with maxima in the insula, basal ganglia, and amygdala. Together, these results support the vulnerability of the glutamatergic system in both bvFTD and AD. Minimal topographical overlap between structural and receptor declines suggest mGluR5 decrements are more extensive than brain atrophy. Furthermore, regional differences between bvFTD and AD indicate disease-specific patterns of glutamatergic neurodegeneration.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".