Study links enzyme to Alzheimer's disease

July 21, 2014
In mice with Alzheimer's-like disease, elevated ASM activity (left) clogs a neuron with cellular waste (arrows) that decreases when levels of ASM are reduced (right). Credit: Lee et al., 2014

Unclogging the body's protein disposal system may improve memory in patients with Alzheimer's disease (AD), according to a study from scientists at Kyungpook National University in Korea published in The Journal of Experimental Medicine.

In AD, various biochemical functions of brain cells go awry, leading to progressive neuronal damage and eventual memory loss. One example is the cellular disposal system, called autophagy, which is disrupted in patients with AD, causing the accumulation of toxic protein plaques characteristic of the disease. Jae-sung Bae and colleagues had earlier noted that the brains of AD patients have elevated levels of an enzyme called acid sphingomyelinase (ASM), which breaks down cell membrane lipids prevalent in the that coats nerve endings. But whether increased ASM directly contributes to AD (and if so, how) was unclear.

The group now finds that these two defects are linked. In mice with AD-like disease, elevated ASM activity clogged up the autophagy machinery resulting in the accumulation of undigested cellular waste. Reducing levels of ASM restored autophagy, lessened brain pathology, and improved learning and memory in the mice. Provided these results hold true in humans, interfering with ASM activity might prove to be an effective way to slow—and possibly reverse—neurodegeneration in with AD.

Explore further: Understanding the molecular mechanisms underlying Alzheimer's disease

More information: Lee, J.K., et al. 2014. J. Exp. Med. DOI: 10.1084/jem.20132451

Related Stories

The benefits of a spotless mind

November 15, 2013

Alzheimer's disease is an age-related memory disorder characterized by the accumulation of clumps of the toxic amyloid-β (Aβ) protein fragment in the extracellular space around neurons in the brain. Drugs that help to 'clean ...

Recommended for you

Predicting change in the Alzheimer's brain

October 6, 2015

MIT researchers are developing a computer system that uses genetic, demographic, and clinical data to help predict the effects of disease on brain anatomy.

Old drug offers new hope to treat Alzheimer's disease

September 21, 2015

Scientists from the Gladstone Institutes have discovered that salsalate, a drug used to treat rheumatoid arthritis, effectively reversed tau-related dysfunction in an animal model of frontotemporal dementia (FTD). Salsalate ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.