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Arch Neurol. 2008 Mar;65(3):323-8. doi: 10.1001/archneurol.2007.64.

Retromer sorting: a pathogenic pathway in late-onset Alzheimer disease.

Author information

1
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. sas68@columbia.edu

Erratum in

  • Arch Neurol. 2008 Jun;65(6):852.

Abstract

During the tail end of the 20th century, a "golden period" in Alzheimer disease (AD) research, many of the pathogenic molecules of the autosomal dominant form of the disease were isolated. These molecular defects, however, do not exist in "sporadic" late-onset AD, the form of the disease that accounts for more than 95% of all cases. Pinpointing the pathogenic molecules of late-onset AD has, therefore, become an urgent goal, both for understanding disease mechanisms and for opening up novel therapeutic avenues. The retromer sorting pathway transports cargo along the endosome-trans-Golgi network, and retromer defects were first implicated in late-onset AD by a study that combined brain imaging with microarray. A range of studies have confirmed that defects in this pathway can play a pathogenic role in the disease. Herein, these findings will be reviewed, the details of the retromer sorting pathway will be discussed, and a biological model that can account for the disease's regional selectivity will be elaborated.

PMID:
18332244
PMCID:
PMC2726781
DOI:
10.1001/archneurol.2007.64
[Indexed for MEDLINE]
Free PMC Article

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