{
  "abstract": "Anti-amyloid antibody treatment for Alzheimer's disease is linked to Amyloid-Related Imaging Abnormalities (ARIA), including vasogenic edema (ARIA-E) and microhemorrhages (ARIA-H), especially in ApoE ε4/4 carriers. To investigate mechanisms underlying ARIA, we examined the binding and temporal vascular effects of immunization with 3D6, the precursor to the anti-amyloid antibody bapineuzumab, in two aged Alzheimer's disease amyloid mouse models. Acutely, 3D6 bound to cerebral amyloid angiopathy (CAA), resulting in C1q binding and classical complement activation. Weekly short-term immunization over 7 weeks resulted in elevated CAA- and plaque-associated complement deposition, red blood cell extravasation and microhemorrhages, and was accompanied by significant transcriptomic changes in genes related to complement, inflammation, vascular dysfunction, and endothelial lipid responses. Longer-term dosing over 13-15 weeks further increased complement deposition and was associated with blood-brain barrier disruption, MMP-9 upregulation, and microhemorrhages, accompanied by reduced amyloid burden and modest CAA clearance. C3 levels correlated with microhemorrhage severity. Perivascular macrophages co-localized with complement-decorated CAA in 3D6-treated mice. These findings implicate complement activation as an early key driver of ARIA and suggest that therapeutic targeting of complement may reduce ARIA risk.",
  "abstract_shown": true,
  "affiliations": [
    "Brigham and Women's Hospital, Boston, MA, USA. pbathini@bwh.harvard.edu",
    "Harvard Medical School, Boston, MA, USA. pbathini@bwh.harvard.edu",
    "Anhalt University of Applied Sciences, Köthen, Germany",
    "Fraunhofer Institute for Cell Therapy and Immunology, Halle (Saale), Germany",
    "Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA",
    "RIKEN Center for Brain Science, Wako, Japan",
    "Brigham and Women's Hospital, Boston, MA, USA. clemere@bwh.harvard.edu",
    "Harvard Medical School, Boston, MA, USA. clemere@bwh.harvard.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Praveen Bathini",
      "orcid": "0000-0002-4031-8975"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Stephan Schilling"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Jens‐Ulrich Rahfeld",
      "orcid": "0000-0002-8979-581X"
    },
    {
      "affs": [
        4
      ],
      "name": "David M. Holtzman",
      "orcid": "0000-0002-3400-0856"
    },
    {
      "affs": [
        5
      ],
      "name": "Takaomi C. Saido",
      "orcid": "0000-0003-1970-6903"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Cynthia Ann Lemere",
      "orcid": "0000-0002-2983-7870"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ag5rz2vm4rcre.bib",
  "cited_by": 6,
  "doi": "10.1186/s13024-026-00965-x",
  "fulltext_url": null,
  "id": "ag5rz2vm4rcre",
  "issns": [
    "1750-1326"
  ],
  "landing_url": "https://doi.org/10.1186/s13024-026-00965-x",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2804|Alzheimer's disease research and treatments"
    ]
  ],
  "openalex": "W7166103028",
  "pdf_url": null,
  "pmcid": "PMC13001455",
  "pmid": "41867862",
  "published": "2026-06-26",
  "publisher": "BioMed Central",
  "ris": "https://research.draconitic.com/paper/ag5rz2vm4rcre.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T13:20:36Z",
      "native_id": "W7166103028",
      "source": "openalex",
      "url": "https://doi.org/10.1186/s13024-026-00965-x"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2804|Alzheimer's disease research and treatments",
      "subfield": "neuroscience"
    }
  ],
  "title": "Early binding of anti-amyloid antibodies to CAA drives complement activation, inflammation and ARIA in mice",
  "title_text": "Early binding of anti-amyloid antibodies to CAA drives complement activation, inflammation and ARIA in mice",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T13:20:49Z",
  "url": "https://research.draconitic.com/paper/ag5rz2vm4rcre",
  "venue": "Molecular Neurodegeneration",
  "versions": []
}