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A research team led by Indiana University School of Medicine scientists has discovered a new method for reducing the formation of amyloid plaques, which disrupt brain function in all aging adults but are particularly prevalent in patients with Alzheimer's disease and related dementias.

The advance, described in a study published in Advanced Science, revolves around the team's development of molecular glue degrader compounds, which bind amyloid precursor protein and its regulatory protein together at their interface in human neurons. These compounds can direct amyloid precursor proteins into the cell's natural disposal areas, the lysosomes, thus eliminating the proteins.

By targeting the proteins that eventually form plaques, the glue degraders could be used therapeutically to reduce the plaques' production. A U.S. patent, "Compounds and methods to treat Alzheimer's disease," has been filed and published by IU.

"Most current approaches to possible amyloid treatment target the plaques after they have been produced, whereas our approach seeks to intervene earlier by selectively reducing amyloid precursor proteins," said Chunhai Hao, M.D., Ph.D., bicentennial professor of pathology and laboratory medicine II and a corresponding author of the study.

" Hao added that the team did not observe any physical or behavioral abnormalities in the mice at the doses tested.

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