Columbia recognizes pathway between Alzheimer's and stroke

William Atkins
Saturday, 19 April 2008 22:57

Science - Biology

The abstract to the Duff paper states:

“Cyclin-dependent kinase 5 (cdk5) has been implicated in Alzheimer's disease (AD) pathogenesis.”

“Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription (STAT1/3) was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels.”

“Furthermore, mice with a targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor.”

“These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis.”

According to the Columbia University Medical Center website, Alzheimer’s disease affects about 4.5 million U.S. citizens. It is divided into early- or late-onset forms.

The early-onset form is rare (and mostly genetic in nature), usually affecting those between the ages of 30 and 60 years.

The late-onset form is much more common, accounting for 90 percent of all cases. It tends to affect those aged 65 years and older.

The occurrance of late-onset Alzheimer’s disease is expected to double in the next 25 years as the U.S. population rapidly ages from the large numbers of people born between 1946 to 1964--the so-called "baby boomer" generation of post-World War II (1939-45).