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Updated: Jun 14, 2026

Stereotaxic Infusion of Oligomeric Amyloid-beta into the Mouse Hippocampus
Published on: June 17, 2015
Interactions between BIM Protein and Beta-Amyloid May Reveal a Crucial Missing Link between Alzheimer's Disease and
Ravit Malishev1, Sukhendu Nandi2, Dariusz Śmiłowicz2
1Department of Chemistry and Ilse Katz Institute for Nanotechnology , Ben-Gurion University of the Negev , Beer-Sheva 84105 , Israel.
Abstract:
Extensive neuronal cell death is among the pathological hallmarks of Alzheimer's disease. While neuron death is coincident with formation of plaques comprising the beta-amyloid (Aβ) peptide, a direct causative link between Aβ (or other Alzheimer's-associated proteins) and cell toxicity is yet to be found. Here we show that BIM-BH3, the primary proapoptotic domain of BIM, a key protein in varied apoptotic cascades of which elevated levels have been found in brain cells of patients afflicted with Alzheimer's disease, interacts with the 42-residue amyloid isoform Aβ42. Remarkably, BIM-BH3 modulated the structure, fibrillation pathway, aggregate morphology, and membrane interactions of Aβ42. In particular, BIM-BH3 inhibited Aβ42 fibril-formation, while it simultaneously enhanced protofibril assembly. Furthermore, we discovered that BIM-BH3/Aβ42 interactions induced cell death in a human neuroblastoma cell model. Overall, our data provide a crucial mechanistic link accounting for neuronal cell death in Alzheimer's disease patients and the participation of both BIM and Aβ42 in the neurotoxicity process.
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