Infectivity of amyloid diseases.
To date, transmissibility of amyloid diseases has not been thoroughly investigated. Although only some of these conformational disorders are considered infectious, all amyloid diseases could be infectious under certain conditions. For transmissibility, endogenous expression of an amyloidogenic peptide required, as well as the presence of an inoculum that is rich in amyloid fibrils and/or their precursors. Notably, administration of one type of amyloid might result in deposition of a different amyloid. Various cofactors could be essential for transmission - some might chaperone the amyloid peptides and/or fibrils, thereby directly facilitating their propagation; others might indirectly stabilize and/or increase levels of conformers with a high beta-sheet content. It is possible that these chaperones are induced by inflammation, which itself can lead to secondary amyloidosis. Thus, amyloid-related therapeutic approaches should not be based on administration of amyloidogenic peptides in conjunction with an inflammatory stimulus, such as in a recently halted clinical trial for Alzheimer's disease.
Sigurdsson
Einar M
EM
Department of Psychiatry, New York University, School of Medicine, 560 First Avenue, New York, NY 10016, USA. einar.sigurdsson@med.nyu.edu
Wisniewski
Thomas
T
Frangione
Blas
B
D000682:Amyloid / Q000378:metabolism; D000686:Amyloidosis / Q000503:physiopathology*; D018562:Disease Transmission, Infectious; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D018832:Molecular Chaperones / Q000378:metabolism
D000682:Amyloid; D006023:Glycoproteins; D018832:Molecular Chaperones; C046748:amyloid enhancing factor