Our Research
Our internationally-known research team has pioneered molecular-level research into the cause, diagnosis, and treatment of Alzheimer’s disease.
We began this field by introducing the hypothesis that the cause of AD is soluble neurotoxins called amyloid β oligomers (AβOs). It was based on our discovery that AβOs
rapidly block synaptic plasticity, the building blocks of memory formation, and ultimately cause the death of brain cells. We have followed our initial discovery with more than 170 papers and patents. It is now widely thought that AβOs, not amyloid plaques, are the Aβ toxins that cause dementia, and they are being studied by hundreds of investigators world-wide.
Our research team at Northwestern is part of an international effort to understand why AβOs build up in the aging brain, to learn how they form and become toxic, to use their buildup to diagnose AD, and to eliminate them from the brain to stop on the onset and progression of Alzheimer’s dementia. We would welcome that chance to discuss our work with you.
Selected contributions to the AβO field from the Klein laboratory:
These and related publications and patents from Klein and collaborators have been cited >35,000 times.
- Introduction of the AβO hypothesis for AD.4.
- Discovery that AβOs impair mechanisms of memory, inhibiting LTP4, 5 and promoting LTD5.
- Determination that brain-derived and synthetic AβOs are structurally homologous.1
- Findings that AβOs induce major facets of AD pathology, including synapse degeneration, tau hyper-phosphorylation, selective nerve cell death, inflammatory glial activation, ER stress, and altered trafficking of receptors and membrane proteins.9-18
- Validation that the AβO hypothesis is disease-relevant, showing AD-dependent buildup of AβOs in human brain and CSF1, 20, 21 and in animal AD models23,
- Discovery that AβOs act as specific ligands that bind to certain synapses.30
- Introduction of the receptor hypothesis as a mechanism for AβO toxicity, with signaling dysfunction impacting Fyn, Arc, Ca++, ROS and ER stress.31, 32
- Introduction of the first AβO-selective antibodies, shared with hundreds of other investigators.33, 34
- Proof that AβO antibodies can be used for MRI and PET imaging in animal AD models.3, 35
- Demonstration that AβO antibodies can rescue memory function in animal AD models.3
- Discovery that transiently expressed AβOs play a role in CNS development.6
- Successful completion of Phase 1 of the “Intercept-AD” clinical trial by Acumen (an Alzheimer’s biotech I co-founded), which tests an AβO monoclonal antibody that was developed based on original research from my team at Northwestern.36, 37
Results of the Intercept AD clinical trial of sabirnetug (ACU193), an aBETA oligomer-targeting antibody.