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Posted by on Apr 4, 2011 in Genetics, Neurology, Neuropsychiatry

New Alzheimer Risk Genes Identified by Huge Collaborative Studies

New Alzheimer Risk Genes Identified by Huge Collaborative Studies


Add up to 5 new gene variants to the 5 that are already known to increase the risk of Alzheimer disease. Newly published data from huge (and I mean huge) genome-association studies in the United States and Europe provide a fresh parade of new high-risk loci*:

  • CD2AP (detected by US group; confirmed by European group)
  • EPHA1 (detected by US group; confirmed by European group)
  • CD33 (detected by US group; confirmed by European group)
  • ABCA7 (detected by US group)
  • MS4A (detected by US group; confirmed by European group)

The US group also replicated previous AD associations at CR1, CLU, BIN1, and PICALM (but not EXOC3L2). And although the risk of AD appears to be increased by 10%-15% with the newly identified loci, this risk pales in comparison to that provided by the variants of the APOE allelewhich can increase the risk of AD by 400%-1000%.

According to the above NCBI links, the function of the proteins of these newly recognized genes are unknown or poorly understood. Consequently their role in AD is even less apparent. EPH receptors (like that produced by EPHA1) “have been implicated in mediating developmental events, particularly in the nervous system,” reveals the gene’s dedicated web page.

The Nature Genetics authors, by way of coverage at GEN (Genetic Engineering and Biotechnology News), write that 5 of the new or previously detected genes (CR1, CLU, EPHA1, CD33, and ABCA7) “have putative functions in the immune system.” Products of BIN1, PICALM, CD33, and CD2AP “are involved in processes at the cell membrane, including endocytosis.” And APOE, CLU, and ABCA7 play some role in lipid processing.

According to Bloomberg, Harvard’s Rudolph Tanzi, one of the 155 authors of the US article, is particularly jazzed about CD33. He muses that some AD-associated variant of the gene may reduce the brain’s capacity to clear beta amyloid, the sheeted protein that accumulates in the illness. Conversely overactivity of the gene may trigger some pathogenic inflammation that causes or contributes to AD. The ultimate hope is that CD33 and the other high-risk loci may provide new targets for AD treatment and prevention. 

Among the lay press reports covering this story is a reasonable review from the NYT‘s Gina Kolata. A more scientifically detailed write-up by the good folks at Nature‘s The Great Beyond blog is awaited.

APOE = apolipoprotein E; NCBI = National Center for Biotechnology Information.

* See the advance online publications from Nature Genetics here and here (subscription required).

Photograph of atrophied brain from person with AD: National Institute on Alcohol Abuse and Alcoholism.

04/05/11 addendum: WTF TGB? No coverage?

bmartin (1127 Posts)

A native East Tennessean, Barbara Martin is a formerly practicing, board-certified neurologist who received her BS (psychology, summa cum laude) and MD from Duke University before completing her postgraduate training (internship, residency, fellowship) at the Hospital of the University of Pennsylvania in Philadelphia. She has worked in academia, private practice, medical publishing, drug market research, and continuing medical education (CME). For the last 3 years, she has worked in a freelance capacity as a medical writer, analyst, and consultant. Follow Dr. Barbara Martin on and Twitter.