Composite
71%
Novelty
35%
Feasibility
48%
Impact
Mechanistic
80%
Druggability
Safety
37%
Confidence
43%

Mechanistic description

Pericyte loss in Alzheimer’s disease leads to proteolytic shedding of PDGFRβ into circulation, providing a blood-accessible marker of pericyte injury. Circulating PDGFRβ correlates with BBB permeability and cognitive decline. Critical weakness: PDGFRβ is not pericyte-specific (expressed on vascular smooth muscle cells, fibroblasts, hepatic stellate cells), making source attribution essential before clinical deployment.

Evidence for (8)

  • Pericyte loss precedes neurodegeneration in AD models

  • Circulating PDGFRβ reflects pericyte coverage in human cohorts

  • PDGFRβ polymorphisms associated with AD risk

  • Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders.

    PMID:22048062 2011 Nat Rev Neurosci
  • The blood-brain barrier in systemic inflammation.

    PMID:26995317 2017 Brain Behav Immun
  • Role of Blood-Brain Barrier in Alzheimer's Disease.

    PMID:29782323 2018 J Alzheimers Dis
  • The blood-brain barrier in Alzheimer's disease.

    PMID:27425887 2017 Neurobiol Dis
  • Blood-Brain Barrier Breakdown in Alzheimer's Disease: Mechanisms and Targeted Strategies.

    PMID:38003477 2023 Int J Mol Sci

Evidence against (3)

  • PDGFRβ+ perivascular fibroblasts distinct from pericytes complicate pericyte-specific attribution

  • Pericyte coverage changes in aging are highly variable and don't always correlate with cognitive outcomes

  • AD risk association was modest (OR ~1.3) and not replicated in independent cohorts

Bayesian persona consensus

58% posterior support

2 signals · 2 for / 0 against · agreement 100%

scidex.consensus.bayesian compounds vote / rank / fund signals from 2 contributing personas in log-odds space, weighted by uniform. Prior 50%.