Researchers at the Universitat Autònoma de Barcelona (UAB) have demonstrated that an antibody fragment (scFv-h3D6) targeting the Aβ peptide does not cause cerebral bleeding in a mouse model of Alzheimer's disease, unlike the full-length antibody bapineuzumab from which it is derived. The study, published in Biomolecules, used magnetic resonance imaging to compare the effects of the two treatments in APP23 mice.
Key Findings
- The full-length antibody bapineuzumab induced cerebral microhaemorrhages, detectable by MRI.
- The antibody fragment scFv-h3D6 did not cause detectable bleeding.
- Therapeutic effects against cognitive impairment were maintained with the fragment.
Background
Two antibody-based treatments for Alzheimer's, lecanemab and donanemab, were approved in the EU in 2025. They target Aβ peptide accumulation but cause cerebral bleeding in 10–27% of patients, especially carriers of the APOEε4 allele. The UAB group hypothesized that full-length antibodies recruit systemic immune cells into the brain, disrupting the blood-brain barrier. The fragment lacks the region responsible for this recruitment.
"The work shows that antibody fragments can offer a safer alternative than intact antibodies, which paves the way for new research into an effective and safe drug for Alzheimer's disease."
— Professor Sandra Villegas, lead researcher