Microglial SPI1 Priming by Circulating C1Q

Mechanistic description

Circulating C1Q from atherosclerotic plaques crosses a compromised blood-brain barrier and primes microglial SPI1 expression, creating neuroinflammatory memory that predisposes to neurodegeneration. Anti-C1Q biologics could prevent this vascular-to-brain inflammatory transmission.

Mechanism / pathway

C1Q
→
neuroinflammation

Evidence for (5)

A lymphocyte-microglia-astrocyte axis in chronic active multiple sclerosis.

PMID:34497421 2021 Nature
Roles of neuropathology-associated reactive astrocytes: a systematic review.

PMID:36915214 2023 Acta Neuropathol Commun
Complement C1q-dependent excitatory and inhibitory synapse elimination by astrocytes and microglia in Alzheimer's disease mouse models.

PMID:37118504 2022 Nat Aging
The neuronal pentraxin Nptx2 regulates complement activity and restrains microglia-mediated synapse loss in neurodegeneration.

PMID:36989373 2023 Sci Transl Med
TREM2 receptor protects against complement-mediated synaptic loss by binding to complement C1q during neurodegeneration.

PMID:37442133 2023 Immunity

Evidence against (3)

Roles of neuropathology-associated reactive astrocytes: a systematic review.

PMID:36915214 2023 Acta Neuropathol Commun
Microglia regulation of synaptic plasticity and learning and memory.

PMID:34472455 2022 Neural Regen Res
Microglial TYROBP/DAP12 in Alzheimer's disease: Transduction of physiological and pathological signals across TREM2.

PMID:36002854 2022 Mol Neurodegener

Evidence matrix

5 supporting 3 contradicting

63% supporting

Supporting

A lymphocyte-microglia-astrocyte axis in chronic active multiple sclerosis. PMID:34497421 · 2021 · Nature
Roles of neuropathology-associated reactive astrocytes: a systematic review. PMID:36915214 · 2023 · Acta Neuropathol Commun
Complement C1q-dependent excitatory and inhibitory synapse elimination by astrocytes and microglia in Alzheimer's disease mouse models. PMID:37118504 · 2022 · Nat Aging
The neuronal pentraxin Nptx2 regulates complement activity and restrains microglia-mediated synapse loss in neurodegeneration. PMID:36989373 · 2023 · Sci Transl Med
TREM2 receptor protects against complement-mediated synaptic loss by binding to complement C1q during neurodegeneration. PMID:37442133 · 2023 · Immunity

Contradicting

Roles of neuropathology-associated reactive astrocytes: a systematic review. PMID:36915214 · 2023 · Acta Neuropathol Commun
Microglia regulation of synaptic plasticity and learning and memory. PMID:34472455 · 2022 · Neural Regen Res
Microglial TYROBP/DAP12 in Alzheimer's disease: Transduction of physiological and pathological signals across TREM2. PMID:36002854 · 2022 · Mol Neurodegener

Cite this hypothesis

Citation

etl-backfill (2026). Microglial SPI1 Priming by Circulating C1Q. SciDEX hypothesis. https://prism.scidex.ai/hypotheses/hyp-SDA-2026-04-08-gap-pubmed-20260406-062122-bfac06c8-3

BibTeX

@misc{scidex_hypothesis_hypsda20,
  title        = {Microglial SPI1 Priming by Circulating C1Q},
  author       = {etl-backfill},
  year         = {2026},
  howpublished = {SciDEX hypothesis},
  url          = {https://prism.scidex.ai/hypotheses/hyp-SDA-2026-04-08-gap-pubmed-20260406-062122-bfac06c8-3},
  note         = {SciDEX artifact hypothesis:hyp-SDA-2026-04-08-gap-pubmed-20260406-062122-bfac06c8-3}
}