ALZHEIMER'S ASSOCIATION
AAIC '26

FLUID BIOMARKERS OF PERICYTE INJURY FOR PRECISION VASCULAR SUBTYPING
David Scott Lewis, Enrique Zueco, Haley Yi
AIXC Bio, Zaragoza, Spain | reports@aixcbio.com

1 INTRODUCTION
Problem & Goals
Healthy Capillary
Blood-brain barrier (BBB)
VS.
Leaky BBB
Anti-amyloid therapy risks
Pericytes injured and vascular therapy risks

BBB breakdown is an early, independent cognitive biomarker preceding amyloid. -> Combinatorial fluid biomarker profile for vascular-dominant Alzheimer's subtypes.

2 METHODS
Workflow & Modeling
CSF + Plasma -> CSF and plasma data aggregated from large cohorts.

Pericytes -> releases -> sPDGFRB
Endothelial cells -> releases -> ANGPT-2

Machine learning classification model
sPDGFRB
ANGPT-2
APOE4
BBB permeability
p-tau217
-> Output
Predicted Subtypes

3 RESULTS
Distinct Subtype & Correlations
(Scatter plot: ANGPT-2, sPDGFRB)
Identification of a distinct MCI subset with elevated ANGPT-2 and sPDGFRB
(Pie chart: APOE4, Bar chart: APOE4)
The profile is highly enriched in APOE4 carriers

neuroimaging
(MRI scans)
correlated with in vivo neuroimaging evidence

standalone p-tau217
MCI n=2533 data
(Line graph)
comparing p-tau217 for amyloid to the distinct vascular decay trajectory predicted by vascular markers

4 CONCLUSIONS
Implications & Key Takeaway
A -> T -> (N)
V
AT(N)+V Framework

Patient stratification
-> Patients
-> Trials

KEY TAKEAWAY
VASCULAR-DOMINANT SUBTYPING USING FLUID PERICYTE & ENDOTHELIAL MARKERS (sPDGFRB/ANGPT-2) ALONGSIDE p-tau217 ENABLES PRECISION NEUROVASCULAR TRIALS.