P1‐111: Development of ultra‐sensitive assay for detection of aggregated beta amyloid in human CSF
Bibliographic record
Abstract
More than 35 million people worldwide have Alzheimer's disease (AD). A major stumbling block to treatment is the absence of robust biomarkers for early detection and monitoring during clinical trials. There is a need for more sensitive and reliable diagnostics to assess the levels of biomarkers in order for current therapeutics to be effective, and for enrollment into clinical trials. Amorfix Life Sciences has developed the EP-AD Diagnostic CSF Test as a quantitative and ultra-sensitive biomarker assay for detection of oligomeric Aβ in human CSF. The EP-AD Diagnostic CSF Test makes use of two methods to isolate and detect oligomeric Aβ while minimizing the signal from monomeric Aβ in CSF. Samples were treated using Epitope Protection (EP) technology to chemically modify epitopes present on the surface of monomeric Ab and prevent antibody recognition. This was followed by affinity-based enrichment of oligomeric Aβ. Oligomeric Aβ was eluted from the enrichment matrix with a disaggregant, and detected using an ultra-sensitive dual bead based immunoassay. Conditions were optimized until the signal from monomeric Ab measured in untreated control CSF (S/N > 600) was reduced below background (S/N < 2.0). Following Epitope Protection and enrichment it was possible to detect a 1/8,000 dilution of a 10% AD brain homogenate spiked into control CSF. Proof-of-concept validation using clinical CSF samples was performed with a blinded panel of twelve (12) samples (6 AD, 6 controls). The EP-AD Test correctly identified 5/6 AD (83% sensitivity) and 5/6 control samples (83% specificity). A second panel of twenty three (23) samples was tested with the following 7/11 AD CSF correctly identified (64% sensitivity) and 9/12 control CSF correctly identified (75% specificity). We have developed methods to minimize the signal from monomeric Aβ, and for specific enrichment of oligomeric Aβ from human CSF. Proof-of-concept validation suggests that this assay shows promise as a potential diagnostic biomarker assay. While the preliminary data is encouraging, further studies with a larger sample set will be required to validate the Amorfix EP-AD Diagnostic CSF Test and evaluate its potential for distinguishing AD from healthy controls, mild cognitive impairment (MCI), and other dementia conditions
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".