Media Releases

Alzheimer’s disease consortium identifies four new genes for alzheimer’s disease risk

April 5, 2011

TORONTO, ON – In the largest study of its kind, an inter­na­tion­al research con­sor­tium includ­ing the Uni­ver­si­ty of Toronto’s Tanz Cen­tre for Research in Neu­rode­gen­er­a­tive Dis­eases, has iden­ti­fied four new genes linked to Alzheimer’s dis­ease.

The research, under­tak­en by the Alzheimer’s Dis­ease Genet­ics Con­sor­tium and report­ed in the cur­rent edi­tion of the jour­nal Nature Genet­ics, details the genet­ic analy­sis of more than 11,000 peo­ple with Alzheimer’s dis­ease and a near­ly equal num­ber of elder­ly peo­ple who have no symp­toms of demen­tia, as well as con­firm­ing data which brings the total num­ber of peo­ple ana­lyzed to 54,000 from the US, Cana­da, the Unit­ed King­dom and Europe.

“Each iden­ti­fied gene adds to the risk of demen­tia lat­er in life. This infor­ma­tion pro­vides great insight into the cause of Alzheimer’s dis­ease,” said Pro­fes­sor Peter St George-Hys­lop, Direc­tor of the Tanz Cen­tre.

The study is the result of a large col­lab­o­ra­tive effort with inves­ti­ga­tors from 44 uni­ver­si­ties and research insti­tu­tions in the Unit­ed States and Cana­da, led by Pro­fes­sor Ger­ard D. Schel­len­berg at the Uni­ver­si­ty of Penn­syl­va­nia, with pri­ma­ry analy­sis sites at Mia­mi, led by Pro­fes­sor Mar­garet A. Per­i­cak-Vance and Boston, led by Pro­fes­sor Lind­sey A. Far­rer with the Cana­di­an cohort col­lec­tion led by Prof. St George-Hys­lop in Toron­to.

Until recent­ly, only four genes asso­ci­at­ed with late-onset Alzheimer’s have been con­firmed, includ­ing SORL1, which was dis­cov­ered at the Tanz Cen­tre  in 2007 (the cur­rent study in Nature Genet­ics also detect­ed a genet­ic asso­ci­a­tion between AD and SORL1). The largest effect on risk of late-onset Alzheimer’s Dis­ease is observed for the e4-allele of the apolipopro­tein E gene (APOE), which was co-dis­cov­ered by Drs. Allen Ros­es, Anne Saun­ders, War­ren Strittmat­ter and Peter St George Hys­lop in 1992.  The Nature Genet­ics study now adds anoth­er four — MS4A, CD2AP, CD33, and EPHA1 — and con­tribute to iden­ti­fy­ing and con­firm­ing two oth­er genes, BIN1 and ABCA7, there­by dou­bling the num­ber of genes known to con­tribute late-onset Alzheimer’s dis­ease.

“This is the cul­mi­na­tion of years of work on Alzheimer’s dis­ease by a large num­ber of sci­en­tists, yet it is just the begin­ning in defin­ing how genes influ­ence mem­o­ry and intel­lec­tu­al func­tion as we age.  We are all tremen­dous­ly excit­ed by our progress so far, but much remains to be done, both in under­stand­ing the genet­ics and in defin­ing how these genes influ­ence the dis­ease process,” Prof. Schel­len­berg said.

In 1992, Prof. St George-Hys­lop and Prof. Don Crap­per McLach­lan report­ed that a pre­vi­ous­ly uniden­ti­fied gene in chro­mo­some 14 caus­es ear­ly-onset of Alzheimer’s dis­ease. In 1995, Prof. St George-Hys­lop led the team which iden­ti­fied this gene on chro­mo­some 14 (pre­se­nilin 1). A few months lat­er he also dis­cov­ered a sec­ond sim­i­lar gene (Pre­se­nilin 2 — locat­ed on chro­mo­some 1), which was respon­si­ble for a less severe form of famil­ial ear­ly-onset Alzheimer’s dis­ease.

The researchers’ ulti­mate aims are two fold.  First, iden­ti­fi­ca­tion of new Alzheimer’s dis­ease genes will pro­vide major clues as to its under­ly­ing cause.  Genet­ic stud­ies can pro­vide new insights into the mol­e­cules at the cen­ter of the dis­ease.  Gain­ing this type of under­stand­ing is crit­i­cal for drug dis­cov­ery since the cur­rent­ly avail­able treat­ments are only mar­gin­al­ly effec­tive.

Sec­ond, gene dis­cov­ery of the type high­light­ed in the Nature Genet­ics arti­cle will con­tribute to pre­dict­ing who will devel­op Alzheimer’s dis­ease, which will be impor­tant when pre­ven­tive mea­sures become avail­able. Know­ing these risk genes will also help iden­ti­fy the first dis­ease-ini­ti­at­ing steps that begin in the brain long before any symp­toms of mem­o­ry loss or intel­lec­tu­al decline are appar­ent.  This knowl­edge will help researchers under­stand the events that lead to the destruc­tion of large parts of the brain and even­tu­al­ly the com­plete loss of cog­ni­tive abil­i­ties.


The research pub­lished in Nature Genet­ics was sup­port­ed by the Nation­al Insti­tute on Aging, part of the Nation­al Insti­tutes of Health, which includes 29 Alzheimer’s Dis­ease Cen­ters, the Nation­al Alzheimer’s Coor­di­nat­ing Cen­ter, the NIA Genet­ics of Alzheimer’s Dis­ease Data Stor­age Site, the NIA Late Onset Alzheimer’s Dis­ease Fam­i­ly Study and the Nation­al Cell Repos­i­to­ry for Alzheimer’s Dis­ease. These Cen­ters col­lect, store and make avail­able to qual­i­fied researchers DNA sam­ples, datasets con­tain­ing bio­med­ical and demo­graph­ic infor­ma­tion about par­tic­i­pants, and genet­ic analy­sis data. The Well­come Trust, Howard Hugh­es, the Alzheimer Soci­ety of Ontario and Cana­di­an Insti­tutes for Health Research sup­port­ed the work done in Cana­da. The Tanz Cen­tre for Research in Neu­rode­gen­er­a­tive Dis­eases is also sup­port­ed by the Fire­fly Foun­da­tion, the Krem­bil Foun­da­tion and the W. Garfield West­on Foun­da­tion.

For more infor­ma­tion, please con­tact:

Paul Can­tin
Asso­ciate Direc­tor, Strate­gic Com­mu­ni­ca­tions,
Uni­ver­si­ty of Toron­to Temer­ty Temer­ty Fac­ul­ty of Med­i­cine
ph: 416–978-2890
Twit­ter: @uoftmedicine