Pericyte-First Sequential Biomarker Cascade — Soluble PDGFR-β as Sentinel Event…

Mechanistic description

CSF soluble PDGFR-β shedding from pericytes as the earliest detectable molecular event in AD, preceding amyloid/tau pathology and exploitable as a ‘zero-stage’ biomarker via ADAM10/17-mediated ectodomain shedding. Biomarker utility is strong; therapeutic translation requires novel PDGFR-β agonism or ADAM10/17-selective CNS inhibition.

Evidence for (5)

Multi-analyte proteomic analysis identifies blood-based neuroinflammation, cerebrovascular and synaptic biomarkers in preclinical Alzheimer's disease.

PMID:39385222 2024 Mol Neurodegener
c-KIT inhibitors reduce pathology and improve behavior in the Tg(SwDI) model of Alzheimer's disease.

PMID:39009412 2024 Life Sci Alliance
Presenilins mediate phosphatidylinositol 3-kinase/AKT and ERK activation via select signaling receptors. Selectivity of PS2 in platelet-derived growth factor signaling.

PMID:16014629 2005 J Biol Chem
Is later-life depression a risk factor for Alzheimer's disease or a prodromal symptom: a study using post-mortem human brain tissue?

PMID:37700368 2023 Alzheimers Res Ther
Associations of plasma SMOC1 and soluble IL6RA levels with the progression from mild cognitive impairment to dementia.

PMID:39640195 2024 Brain Behav Immun Health

Evidence against (2)

PMID:35033164 Wang J et al., Mol Neurodegener 2022 Jan 15
PMID:39085945 Preis L et al., Alzheimers Res Ther 2024 Jul 31

Evidence matrix

5 supporting 0 contradicting

100% supporting

Supporting

Multi-analyte proteomic analysis identifies blood-based neuroinflammation, cerebrovascular and synaptic biomarkers in preclinical Alzheimer's disease. PMID:39385222 · 2024 · Mol Neurodegener
c-KIT inhibitors reduce pathology and improve behavior in the Tg(SwDI) model of Alzheimer's disease. PMID:39009412 · 2024 · Life Sci Alliance
Presenilins mediate phosphatidylinositol 3-kinase/AKT and ERK activation via select signaling receptors. Selectivity of PS2 in platelet-derived growth factor signaling. PMID:16014629 · 2005 · J Biol Chem
Is later-life depression a risk factor for Alzheimer's disease or a prodromal symptom: a study using post-mortem human brain tissue? PMID:37700368 · 2023 · Alzheimers Res Ther
Associations of plasma SMOC1 and soluble IL6RA levels with the progression from mild cognitive impairment to dementia. PMID:39640195 · 2024 · Brain Behav Immun Health

Contradicting

No contradicting evidence recorded.

Cite this hypothesis

Citation

etl-backfill (2026). Pericyte-First Sequential Biomarker Cascade — Soluble PDGFR-β as Sentinel Event…. SciDEX hypothesis. https://prism.scidex.ai/hypotheses/h-f78f8262

BibTeX

@misc{scidex_hypothesis_hf78f826,
  title        = {Pericyte-First Sequential Biomarker Cascade — Soluble PDGFR-β as Sentinel Event…},
  author       = {etl-backfill},
  year         = {2026},
  howpublished = {SciDEX hypothesis},
  url          = {https://prism.scidex.ai/hypotheses/h-f78f8262},
  note         = {SciDEX artifact hypothesis:h-f78f8262}
}