UCLA researchers in the Department of Neurology have developed a novel immunotherapy targeting a previously unexplored pathway of Aβ toxicity in Alzheimer’s disease.
Alzheimer’s disease (AD) is a major global healthcare challenge, with dementia-related costs estimated at over $600 billion worldwide. Yet development of AD therapies has encountered minimal success, and the cause of the disease is still mostly unknown. One approach toward treatment has been to develop immunotherapies that target and remove the buildup of amyloid beta (Aβ) plaques in the brain that are associated with AD. However, these immunotherapies have had limited success in clinical trials, leading researchers to search for alternate pathways that lead to neurodegeneration. To develop truly effective AD treatment, there is significant need for specific and targeted therapies that focus on novel or underexplored neurotoxic mechanisms.
UCLA researchers have developed an immunotherapy that targets an alternate mechanism of amyloid beta (Aβ) toxicity for the treatment of Alzheimer’s disease (AD). Specific Aβ variants have been shown to inhibit ADAM10, an enzyme that produces the neuroprotective peptide sAPPα, which is involved in the maintenance of memory. Treatment with antibodies for these Aβ peptidesactivates the immune system to selectively remove the neurotoxic fragments and restore neuroprotection. This immunotherapy does not affect amyloid plaques and therefore avoids the severe side effect of amyloid-related imaging abnormalities often found in AD immunotherapy.
Successful demonstration that select Aβ variants and chiral substitutions have differing selectivity for ADAM10, the enzyme of interest that generates soluble amyloid precursor protein alpha (sAPPα). Future work will focus on raising antibodies against these Aβ variants.
immunotherapy; alzheimer’s; central nervous system; antibody; amyloid beta; amyloid precursor protein