Evidence mapPaperPMID 41398960Full record

ReviewMolecular neurodegeneration2025

The complement cascade in Alzheimer's disease: modern implications of an ancient immune protagonist.

Maria-Tzousi Papavergi, Praveen Bathini, Brijendra Singh, Cynthia A Lemere

Abstract readReview
In one paragraph

Review in Molecular neurodegeneration, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Maria-Tzousi Papavergi *Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. mtzousipapavergi@bwh.harvard.edu.
Praveen Bathini *Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Brijendra Singh *Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Cynthia A LemereAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. clemere@bwh.harvard.edu.

Funding

Understanding and Mitigating Vascular Side-Effects Associated with Anti-Amyloid ImmunotherapyR01NS136122 · BRIGHAM AND WOMEN'S HOSPITAL · 2025 to 2025
$784k
NINDS NIH HHS R01 NS136122
6 · The paper itself

Abstract

The complement system, a critical arm of innate immunity, has emerged as a key contributor to the pathogenesis of Alzheimer’s disease (AD). While complement-mediated synaptic pruning is essential during brain development, its reactivation in the aging and diseased brain can promote neurodegeneration. In AD and cerebral amyloid angiopathy (CAA), aberrant complement activity contributes to amyloid-β (Aβ) accumulation, synapse loss, neuroinflammation, vascular dysfunction and blood-brain barrier (BBB) disruption. This review traces the evolving understanding of complement dysregulation in AD, from foundational findings in human studies to mechanistic discoveries in animal models and emerging induced pluripotent stem cell (iPSC)-derived cellular systems. It describes how genetic and epigenetic factors, including risk variants, chromatin modifications, and microRNAs, modulate complement pathways in the AD brain. Systemic influences, such as gut-brain axis disruption, are also considered for their potential to exacerbate complement-mediated neuroinflammation in AD. We further highlight efforts to identify biomarkers of complement activation and review the therapeutic potential of targeting complement components and regulators. By integrating molecular, experimental, and translational perspectives, this review outlines the multifaceted involvement of complement in AD and discusses key directions for future research and therapeutic interventions.

Indexed as

Alzheimer DiseaseComplement ActivationComplement System ProteinsAnimalsBrainHumansComplement System Proteins

Identifiers

PMID41398960
PMCPMC12821280

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.