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

Understanding the molecular mechanisms underlying Alzheimer's disease

June 10, 2013
The accumulation of amyloid-β (Aβ) in the brains of Alzheimer's disease (AD) patients is known to be associated with memory loss and neuronal degeneration, but the mechanism of Aβ pathogenesis is not fully understood.

Drug's effect on Alzheimer's may depend on severity of disease

July 16, 2014
A cancer drug that has shown promise against Alzheimer's disease in mice and has begun early clinical trials has yielded perplexing results in a novel mouse model of AD that mimics the genetics and pathology of the human ...

Study examines association between small-vessel disease, Alzheimer pathology

May 12, 2014
Cerebral small-vessel disease (SVD) and Alzheimer disease (AD) pathology appear to be associated.

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 ...

Enzyme BACE1 may be important in predicting onset of Alzheimer disease

December 12, 2013
The critical enzyme beta-secretase1 (BACE1) is known to be elevated in brains with sporadic Alzheimer disease (AD). Scientists have now found increased levels of BACE1 in brains with mild cognitive impairment (MCI), suggesting ...

Key cellular auto-cleaning mechanism mediates the formation of plaques in Alzheimer's brain

October 3, 2013
Autophagy, a key cellular auto-cleaning mechanism, mediates the formation of amyloid beta plaques, one of the hallmarks of Alzheimer's disease. It might be a potential drug target for the treatment of the disease, concludes ...

Recommended for you

Lifestyle changes to stave off Alzheimer's? Hints, no proof

July 20, 2017
There are no proven ways to stave off Alzheimer's, but a new report raises the prospect that avoiding nine key risks starting in childhood just might delay or even prevent about a third of dementia cases around the world.

Steering an enzyme's 'scissors' shows potential for stopping Alzheimer's disease

July 19, 2017
The old real estate adage about "location, location, location" might also apply to the biochemical genesis of Alzheimer's disease, according to new research from the University of British Columbia.

Brain scans may change care for some people with memory loss

July 19, 2017
Does it really take an expensive brain scan to diagnose Alzheimer's? Not everybody needs one but new research suggests that for a surprising number of patients whose memory problems are hard to pin down, PET scans may lead ...

Can poor sleep boost odds for Alzheimer's?

July 18, 2017
(HealthDay)— Breathing problems during sleep may signal an increased risk for Alzheimer's disease, a trio of studies suggests.

Hearing is believing: Speech may be a clue to mental decline

July 17, 2017
Your speech may, um, help reveal if you're uh ... developing thinking problems. More pauses, filler words and other verbal changes might be an early sign of mental decline, which can lead to Alzheimer's disease, a study suggests.

Bacteria found in Alzheimer's brains

July 17, 2017
Researchers in the UK have used DNA sequencing to examine bacteria in post-mortem brains from patients with Alzheimer's disease. Their findings suggest increased bacterial populations and different proportions of specific ...

0 comments

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.