[P3–195]: PROFILING EXOSOMAL MIRNAS IN EARLY ONSET ALZHEIMER's DISEASE CEREBROSPINAL FLUID
Bibliographic record
Abstract
Early onset Alzheimer's disease (EOAD) occurs before the age of 65 and represents 5–10% of all AD cases. EOAD and late onset AD share amyloid and tau pathology but there are important differences between the two with respect to age of onset, speed of progression and presenting symptoms. Since EOAD is only rarely caused by autosomal dominant mutation inheritance, there are currently no distinguishing biomarkers for EOAD alone. MicroRNAs (miRNAs) are short non-coding RNAs involved in the degradation or translational repression of several mRNA targets. MiRNAs are packaged into exosomes, released by cells into the extracellular milieu and biofluids, including cerebrospinal fluid (CSF), and are implicated in cell-to-cell communication. We hypothesized that uncovering significantly altered exosomal miRNAs in the CSF of EOAD patients would reveal novel biomarkers, provide insight into disease mechanism, and guide therapeutic development. CSF was obtained by lumbar puncture from patients diagnosed with EOAD (n=17, 60.88±4.62 years) and healthy controls (n=12; 67.08±7.83 years). The miRCURYExosome Isolation Kit (Exiqon) was used to isolate exosomes from 1.0mL of input CSF. Subsequently, the miRNA was purified from each exosomal prep and converted into cDNA. For the discovery phase of the study, each sample underwent real-time PCR on two 384 well plates with 752 miRNA primer sets (Exiqon Human Panels I and II), whereby candidate differentially expressed miRNAs were revealed. For the validation phase, candidate miRNAs are being confirmed by independent real-time PCR experiments. Preliminary data from the discovery phase revealed that of 52 miRNAs expressed in at least 75% of all samples, 7 were up-regulated and 10 were down-regulated in the exosomal CSF from EOAD compared with healthy controls (all p<0.05). To date, the down-regulation of miR-451a in EOAD has been validated (p<0.01). Computational modeling is being performed to assess whether multiple differentially expressed miRNAs can predict EOAD diagnosis. Also, a bioinformatics analysis is being conducted to identify putative mRNA targets and pathways altered in EOAD. This study identified novel differentially expressed exosomal miRNAs from CSF isolated from EOAD patients. These miRNAs may differentiate EOAD from other forms of AD, elucidate disease mechanism, and contribute novel targets for therapeutics.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".