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Wednesday, Feb 01, 2023

HKUST team finds key protein in Alzheimer's disease puzzle

HKUST team finds key protein in Alzheimer's disease puzzle

Scientists at the Hong Kong University of Science and Technology led by incoming president Nancy Ip Yuk-yu have identified a blood protein that plays a key role in the pathogenesis of Alzheimer's disease - a discovery that could help treat millions of suffers.
There are currently 50 million people suffering from the disease worldwide, with the number expected to double in two decades.

Researchers had previously found that memory loss and cognitive problems, two major characteristics of Alzheimer's patients, were caused by cellular dysfunction, where immune cells (microglia) in the brain could not clear the toxic amyloid-beta peptides. The reason behind this impairment is still not understood.

Also, with the increase of age, A? deposits occur more in the brain due to a reduction in the microglial clearance of A?.

The same research team - led by Ip - had earlier found that cytokine interleukin-33 is helpful for the microglial clearance of A? in the brain. This time, they have discovered that reducing the level of a blood protein named soluble ST2, which plays a key role in disrupting A? clearance by microglia, can counter the disease's development and ameliorate Alzheimer's-related pathologies in patients.

Compared to other therapeutic strategies targeting the brain, this innovative treatment is a simpler and safer approach and only requires manipulation of the protein in the blood, researchers said.

"While this exciting work has further improved our understanding of Alzheimer's and identified an excellent drug target for developing therapeutics," said Ip, "it has also made clear the importance of precision medicine in tackling this complex, multifactorial disease."

The researchers also found people carrying a genetic variant termed "rs1921622" are less likely to suffer from Alzheimer's , even as they age, because the sST2 levels in their blood are relatively low.

The correlation between sST2 levels and genetic factors is particularly keen in women carrying the APOE4 gene, who not only bear a higher risk of developing AD, but also show severe symptoms.

The strategy opens up new possibilities for women carrying APOE4, accounting for 25 to 50 percent of all Alzheimer's patients.

The study was recently published in the journal Nature Aging.

Ip said: "The next step is to develop clinical interventions that target sST2 and determine their viability as effective Alzheimer's preventatives and treatments, especially for female APOE4 carriers who are at high risk of developing Alzheimer's."

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