Trisomy Disorders

A Human Stem Cell Model of Early Alzheimer’s Disease Pathology in Down Syndrome.

Posted on: February 25, 2012

A Human Stem Cell Model of Early Alzheimer’s Disease Pathology in Down Syndrome.

Feb 2012

Source

Gurdon Institute and Department of Biochemistry, University of Cambridge,Tennis Court Road, Cambridge, CB2 1QN.

Abstract

Human cellular models of Alzheimer’s disease (AD) pathogenesis would enable the investigation of candidate pathogenic mechanisms in AD and the testing and developing of new therapeutic strategies. We report the development of AD pathologies in cortical neurons generated from human induced pluripotent stem (iPS) cells derived from patients with Down syndrome. Adults with Down syndrome (caused by trisomy of chromosome 21) develop early-onset Alzheimer’s disease, probably due to increased expression of a gene on chromosome 21 that encodes the amyloid precursor protein (APP). We found that cortical neurons generated from iPS cells and embryonic stem (ES) cells from Down syndrome patients developed AD pathologies over months in culture, rather than years in vivo. These cortical neurons processed the transmembrane APP protein resulting in secretion of the pathogenic peptide fragment amyloid-β42 (Aβ42), which formed insoluble intracellular and extracellular amyloid aggregates. Production of Aβ peptides was blocked by a gamma-secretase inhibitor. Finally, hyperphosphorylated tau protein, a pathological hallmark of AD, was found to be localized to cell bodies and dendrites in iPS cell-derived cortical neurons from Down syndrome patients, recapitulating later stages of the AD pathogenic process.

Sciencemag.org

 

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

February 2012
M T W T F S S
« Sep   Mar »
 12345
6789101112
13141516171819
20212223242526
272829  

Blog Stats

  • 79,223 hits

Top Posts

%d bloggers like this: