[P3–425]: ELEVATED CSF LEVELS OF NEUROFILAMENT LIGHT CHAIN IS ASSOCIATED WITH GRAY MATTER NEURODEGENERATION IN BOTH HUMANS AND TRANSGENIC RAT MODEL OF ALZHEIMER's DISEASE
Bibliographic record
Abstract
The cerebrospinal fluid (CSF) neurofilament light (NfL) is a part of major neuronal cytoskeletons. Recent findings have revealed elevated CSF-NfL levels in subjects with neurodegenerative disease (FTD, ALS, AD) and APPPS1 transgenic mouse model, suggesting its role as a novel disease severity marker. However, its association with in vivo imaging disease severity markers, such as gray matter density in AD is still elusive. Here, we aim to investigate the link between CSF-NfL and VBM in AD patients as well as DBM in McGill-R-Thy1-APP transgenic (Tg) rats. We hypothesize that the CSF-NfL level is associated with the atrophy of AD-vulnerable regions in both humans and animals. 40 MCI and 50 AD patients from Alzheimer's Disease Neuroimaging Initiative (ADNI) and 12 Tg rats were assessed. In humans, baseline CSF-NfL and 24-month modulated VBM from ADNI database was used. Tg rats underwent CSF collection at 17 months; CSF-NfL concentration was measured using a novel ultrasensitive Single molecule array (Simoa) method. Also, structural MRI with FISP at TR/TE = 2.5/5.0ms was performed at 21 months. DBM was generated from the linear and nonlinear transformations to standard space. The statistical analysis of voxel-wise parametric map was performed using VoxelStats using the following models: Human: VBM ∼ CSF-NFL + Gender + Education + APOE + Age Tg rat: DBM ∼ NFL17mo. In humans, the CSF-NfL level was negatively associated with VBM in the PCC, precuneus, basal temporal lobes, supramarginal gyrus, lateral frontal gyrus, and parahippocampal regions in both MCI and AD groups. In addition, Tg rat CSF-NfL was negatively associated, in both grey and white matter, with the corpus callosum, parietotemporal cortex, entorhinal cortex, PCC, hippocampus, nucleus accumbens, thalamus, striatum, and midbrain regions.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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 | 0.001 |
| 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 teacher head, 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".