%0 Journal Article
%T Recent Alzheimer's disease research highlights
%A Douglas Galasko
%A Todd Golde
%A Gordon Wilcock
%J Alzheimer's Research & Therapy
%D 2012
%I BioMed Central
%R 10.1186/alzrt117
%X For many years the lack of truly faithful cellular and animal models of AD has imposed some limitation on what can be inferred from these experimental models. With the technological advances demonstrating that human fibroblasts can be converted into pluripotent stem (iPS) cells and subsequently into neurons, and the promise of this technology to provide new cellular models of human neurodegenerative disease, it was only a matter of time for this technology to be applied to the study of AD.Over the past year, the first of what are likely to be a plethora of studies examining culture models of AD based on neuronally differentiated iPS cells derived from familial and sporadic AD patients and Down syndrome were published. The first of these demonstrated that fibroblasts from familial AD patients with presenilin 1 or 2 mutations showed altered processing of amyloid ¦Â protein precursor (APP) and increased production of total amyloid ¦Â protein (A¦Â) with increased relative production of A¦Â42 [1]. The second included neuronally differentiated iPS cells from reprogrammed fibroblasts of two APP gene duplication carriers, two patients with sporadic AD and two controls [2]. In the neuronally differentiated iPS cell lines from familial and one of the two sporadic AD patients, there was higher secretion of A¦Â40. A further finding in these three AD cell lines provided a suggestion of interactions with mechanisms of tau pathology: higher levels of phospho-tau and active glycogen synthase kinase (GSK)3¦Â. The third and most recent paper conducted similar studies using neuronally differentiated iPS cells from Trisomy 21 patients [3].When differentiated, these cells showed increased production of A¦Â42, increased phospho-tau and perhaps most interesting, the accumulation of A¦Â42 aggregates.Although the alterations in APP and A¦Â observed were largely anticipated, based on previous data from human fibroblasts and other biological samples [4], the alterations in tau and GSK3¦Â activity are s
%U http://alzres.com/content/4/3/14