Before the cardiologist goes nuclear w/ stress #AHA17

Measuring troponin in CAD patients before embarking on stress testing may provide Read more

Virus hunting season open

Previously unknown viruses, identified by Winship + UCSF scientists, come from a patient with a melanoma that had metastasized to the Read more

#AHA17 highlight: cardiac pacemaker cells

Highlighting new research on engineering induced pacemaker cells from Hee Cheol Cho's Read more

plaques

The secrets of a new Alzheimer’s secretase

The title of Keqiang Ye’s recent Nature Communications paper contains a provocative name for an enzyme: delta-secretase.

Just from its name, one can tell that a secretase is involved in secreting something. In this case, that something is beta-amyloid, the toxic protein fragment that tends to accumulate in the brains of people with Alzheimer’s disease.

Aficionados of Alzheimer’s research may be familiar with other secretases. Gamma-secretase was the target of some once-promising drugs that failed in clinical trials, partly because they also inhibit Notch signaling, important for development and differentiation in several tissues. Now beta-secretase inhibitors are entering Alzheimer’s clinical trials, with similar concerns about side effects.

Many Alzheimer’s researchers have studied gamma- and beta-secretases, but a review of the literature reveals that so far, only Ye and his colleagues have used the term delta-secretase.

This enzyme previously was called AEP, for asparagine endopeptidase. AEP appears to increase activity in the brain with aging and cleaves APP (amyloid precursor protein) in a way that makes it easier for the real bad guy, beta-secretase, to produce bad beta-amyloid.*At Alzforum, Jessica Shugart describes the enzyme this way:

Like a doting mother, AEP cuts APP into bite-sized portions for toddler BACE1 [beta-secretase] to chew on, facilitating an increase in beta-amyloid production. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Untangling the mysteries of Alzheimer’s disease

Lary Walker, PhD

Consider this: Alzheimer’s is a uniquely human disorder. But why? Why don’t nonhuman primates, such as monkeys, get Alzheimer’s disease. Monkeys form the senile plaques that are identical to the plaques found in humans. So do other animals.

“Yet, despite the fact that nonhuman primates make this protein that we know is very important in the pathogenesis of Alzheimer’s disease, they don’t develop the full disease,” says Lary Walker, PhD. Walker is an associate professor at Yerkes National Primate Research Center.

“They don’t develop the tangles we associate with Alzheimer’s disease, the neuronal loss, the shrinkage of the brain, and they don’t get demented in the sense that humans do,” says Walker.

When our bodies make a protein, the protein tends to fold into a functional form. But when it comes to Alzheimer’s disease, some proteins misfold, becoming sticky and then combining with one another. In their collective form, the proteins can then form plaques or tangles, the two types of lesions associated with Alzheimer’s disease.

And for some unknown reason, people who have plaques usually go on to form tangles. But people who have tangles don’t always go on to form plaques. No one is sure why. But that’s what researcher Walker wants to find out.

To listen to Walker’s own words about Alzheimer’s disease, access Emory’s new Sound Science podcast.

Posted on by Robin Tricoles in Neuro Leave a comment