New treatment reverses Alzheimer’s disease signs

According to a preclinical study from Penn Medicine researchers, a molecular compound mimics the effect of natural chaperones that are depleted in the aging brain.

Sheets of brain scans.
Image: iStock/Nomadsoul1

A “chaperone” molecule that slows the formation of certain proteins reversed disease signs, including memory impairment, in a mouse model of Alzheimer’s disease, according to a study from researchers at the Perelman School of Medicine.

In the study, published in Aging Biology, researchers examined the effects of a compound called 4-phenylbutyrate (PBA), a fatty-acid molecule known to work as a “chemical chaperone” that inhibits protein accumulation. In models of Alzheimer’s disease, injections of PBA helped to restore signs of normal proteostasis (the protein regulation process) in brains while also dramatically improving their performance on a standard memory test, even when administered late in the disease course.

“By generally improving neuronal and cellular health, we can mitigate or delay disease progression,” says study senior author Nirinjini Naidoo, a research associate professor of sleep medicine. “In addition, reducing proteotoxicity—irreparable damage to the cell that is caused by an accumulation of impaired and misfolded proteins—can help improve some previously lost brain functions.”

The team discovered that they could achieve similar effects, including the reversal of memory deficits, even starting in middle age.

Both early-life and middle-age treatment showed signs of inhibiting the process that forms the most prominent protein aggregates in Alzheimer’s, known as amyloid beta plaques. For the later treatment, not only the underlying process but also the amyloid plaque numbers themselves were reduced.

Read more at Penn Medicine News.