Neuromag November 2017 | Page 15

stop the cascade of events leading to cognitive decline . Our results add another dimension to this argument by pointing to the fact that Aβ produced early in disease may be exceptional not only in the time it appears but also in its biochemical features and potency . We argue that it is crucial to intervene as early as possible in AD to have a chance at changing the course of this devastating disease . To implement these strategies , extremely sensitive biomarkers will need to be discovered in order to zoom in on this critical window .
Figure 3 . Total seeding dose 50 plateaus with increasing age while the specific activity peaks at the age of deposition in both mouse lines . Adapted from Ye et al .
Jay Rasmussen is a PhD candidate in the Hertie Institute for Clinical Brain Research in the lab of Prof . Dr . Mathias Jucker in Tübingen , Germany .
Article written in reference to : Ye L , Rasmussen J , Kaeser SA , Marzesco A , Obermueller U , Mahler J , Schelle J , Odenthal J , Krueger C , Fritschi SK , Walker LC , Staufenbiel M , Baumann F and Jucker M . Aβ seeding potency peaks in the early stages of cerebral β-amyloidosis . EMBO Reports . 2017 ( in press ).
References : [ 1 ] www . WHO . int [ 2 ] Hardy J , Selkoe DJ . The amyloid hypothesis of Alzheimer ’ s disease : progress and problems on the road to therapeutics . Science 2002 ; 297 : 353-6 . [ 3 ] Bateman RJ , et al . Clinical and biomarker changes in dominantly inherited Alzheimer ' s disease . NEJM 2012 ; 367 : 795-804 . [ 4 ] Glenner GG , Wong CW . Alzheimer ’ s disease : initial report of the purification and characterization of a novel cerebrovascular amyloid protein . BBRC 1984 ; 120 : 885-90 . [ 5 ] Masters CL , et al . Amyloid plaque core protein in Alzheimer disease and Down syndrome . PNAS USA 1985 ; 82 : 4245-9 . [ 6 ] Bolduc DM , et al . The amyloid-beta forming tripeptide cleavage mechanism of gamma-secretase . Elife 2016 ; 5 : e17578 . [ 7 ] Jarrett JT , Lansbury PT , Jr . Seeding “ one-dimensional crystallization ” of amyloid : a pathogenic mechanism in Alzheimer ’ s disease and scrapie ? Cell 1993 ; 73 : 1055-8 . [ 8 ] Eisenberg D , Jucker M . The amyloid state of proteins in human diseases . Cell 2012 ; 148 : 1188-203 . [ 9 ] Jucker M , Walker LC . Self-Propagation of pathogenic protein aggregates in neurodegenerative disease . Nature 2013 ; 501:45-51 . [ 10 ] Meyer-Luehmann M , et al . Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and host . Science 2006 ; 313 : 1781-4 . [ 11 ] Watts JC , et al . Bioluminescence imaging of Abeta deposition in bigenic mouse models of Alzheimer ’ s disease . PNAS USA 2011 ; 108 : 2528-33 . [ 12 ] Morales R , et al . De novo induction of amyloid-beta deposition in vivo . Mol . Psychiatry 2012 ; 17 : 1347-53 . [ 13 ] Rasmussen J , et al . Aβ Seeds and Prions : How Close the Fit ? Prion 2017 ( in press ). [ 14 ] Heilbronner G , et al . Seeded strain-like transmission of beta-amyloid morphotypes in APP transgenic mice . EMBO Reports 2013 ; 14 : 1017-22 . [ 15 ] Suzuki N , et al . An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor ( beta APP717 ) mutants . Science 1994 ; 264 : 1336-40 . [ 16 ] Scheuner D , et al . Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer ' s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer ' s disease . Nat . Med . 1996 ; 2 : 864-70 . [ 17 ] Ryman DC , et al . Symptom onset in autosomal dominant Alzheimer disease : a systematic review and meta-analysis . Neurology 2014 ; 83 : 253-60 .
November 2017 | NEUROMAG | 15