Plasma amyloid-beta ratio reflects brain amyloid plaque pathology
PrimaryC2N's PrecivityAD theory is that altered plasma amyloid-beta 42/40, measured with high-resolution mass spectrometry, can serve as a blood-based proxy for amyloid plaques in the brain, a defining pathology of Alzheimer's disease. The causal disease model is that amyloid plaque accumulation is part of Alzheimer's pathobiology and can identify patients whose cognitive impairment is likely due to Alzheimer's disease rather than another cause. Testable predictions are that PrecivityAD blood classifications should agree with amyloid PET classifications, identify PET-positive patients with high positive predictive value, and be usable for selecting patients who may benefit from amyloid-targeting therapies.
Popperian evaluation
The premise is credible: amyloid plaque burden is a defined Alzheimer's pathology, amyloid PET is a reasonable reference for in vivo plaque positivity, and plasma amyloid-beta 42/40 measured by high-resolution mass spectrometry has a plausible link to brain amyloid status. The theory is strongest as a classification claim against PET, not as a full causal explanation of cognitive impairment.
Supporting evidence: PrecivityAD showed 80.7% overall agreement with florbetapir amyloid PET in 537 Bio-Hermes participants with mild cognitive impairment or mild dementia.; PrecivityAD identified florbetapir PET-positive patients with 86.0% positive predictive value.; Amyloid plaque accumulation is treated in the evidence set as a defining Alzheimer's disease pathology.
Counter evidence: The theory depends on amyloid PET as the reference standard, which tests plaque positivity rather than the full cause of a person's cognitive symptoms.; In the exploratory Down syndrome cohort, amyloid-beta 42 and amyloid-beta 40 were less informative than p-tau217, although that cohort was small.
The theory explains the main observed pattern well: a blood amyloid-beta 42/40 classification tracks amyloid PET status often enough to support triage or therapy-selection use. It does not fully explain Alzheimer's diagnosis, disease progression, or cognitive decline, because amyloid positivity is one pathology marker and p-tau217 appears stronger in some related evidence.
Supporting evidence: Blood classifications agreed with florbetapir PET classifications at 80.7% overall agreement.; The test selected PET-positive patients with 86.0% positive predictive value.; Bio-Hermes results supported plasma biomarker stratification as interchangeable with amyloid PET criteria for selecting patients who may benefit from amyloid-targeting therapies.
Counter evidence: p-tau217 had higher agreement with florbetapir PET in the same Bio-Hermes context, 90.1% versus 80.7% for PrecivityAD.; Plasma p-tau217 progression showed temporal associations with amyloid PET, tau PET, and cognitive decline, which may explain disease progression better than amyloid-beta ratio alone.; A positive amyloid signal does not by itself prove that a patient's cognitive impairment is due to Alzheimer's disease rather than mixed or non-Alzheimer's causes.
This is a clearly testable theory. It makes numeric, refutable predictions against amyloid PET: agreement, positive predictive value, and non-inferiority at a defined PET threshold. A failed prospective cohort, weak agreement in the intended-use population, or poor enrichment for PET-positive patients would directly damage the claim.
Supporting evidence: The theory predicts high agreement between PrecivityAD blood classifications and amyloid PET classifications.; The theory predicts high positive predictive value for identifying PET-positive patients.; The evidence tested non-inferiority to quantitative florbetapir PET at 37 Centiloids for identifying positive PET visual reads.
Counter evidence: The therapy-selection claim is less directly falsified unless studies measure treatment eligibility or treatment outcomes, rather than PET status alone.; Performance may vary by population, as suggested by the small Down syndrome cohort where amyloid-beta 42 and amyloid-beta 40 were less informative.
Reasoning tree
Public endorsements
The evidence ties Ilana Fogelman to C2N's formation through LTR, but it does not show any public statement from her about PrecivityAD, plasma amyloid-beta 42/40, amyloid PET concordance, or Alzheimer's plaque biology. On this record, she stays silent on the theory itself.
The provided evidence shows Joel B. Braunstein is C2N's co-founder and CEO and describes C2N's general mission, but it does not show him publicly discussing the specific theory that plasma amyloid-beta 42/40 tracks brain amyloid plaque pathology or that PrecivityAD should align with amyloid PET and guide amyloid-targeting therapy selection.
The supplied evidence shows company-related publications about PrecivityAD and blood biomarkers, but it does not contain any quote, record, or attributed publication from Justine Coppinger herself. On this dossier, there is no public statement from her endorsing, mentioning, or contradicting the theory.
The supplied evidence does not show this person discussing C2N's plasma amyloid-beta 42/40 theory at all. The quote snippets are about Myrtle Beach real estate and off-market property investing, and the C2N team page excerpt does not provide a public statement from this person on PrecivityAD or amyloid plaque biology.
The evidence places Philip Verghese at C2N and names him as an inventor on a C2N patent, but neither record says anything about the PrecivityAD theory, plasma amyloid-beta 42/40, amyloid PET agreement, or blood-based detection of brain amyloid plaques. On this record, he is publicly associated with the company, not publicly endorsing or contradicting this specific theory.