Tol2 gene trap integrations in the zebrafish amyloid precursor protein genes appa and aplp2 reveal accumulation of secreted APP at the embryonic veins

Abstract

Background-The single spanning transmembrane amyloid precursor protein (APP) and its proteolytic product, amyloid-beta (Aβ) peptide, have been intensely studied due to their role in the pathogenesis of Alzheimer's disease. However, the biological role of the secreted ectodomain of APP, which is also generated by proteolytic cleavage, is less well understood. Here, we report Tol2 red fluorescent protein (RFP) transposon gene trap integrations in the zebrafish amyloid precursor protein a (appa) and amyloid precursor-like protein 2 (aplp2) genes. The transposon integrations are predicted to disrupt the appa and aplp2 genes to primarily produce secreted

Evidence For and Against a Pathogenic Role of Reduced γ-Secretase Activity in Familial Alzheimer’s Disease

“…A␤PP has also been shown to have a very wide range of cellular functions. A␤PP influences Fe ion homeostasis via its interaction with Ferroportin (SLC40A1, [125]) and A␤PP affects embryo development, including vascular development, possibly via secretion of its extracellular/luminal domain [126,127] and A␤ [128]. A␤PP also influences the rate of protein synthesis [129], neurite outgrowth [130], and axonal pruning [131] as well as LPSmediated innate immune responses [132].…”

Research progress in animal models and stem cell therapy for Alzheimer’s disease

“…As a vertebrate model, zebrafish has been used to reveal particular characteristics of the various genes implicated in AD, which have been difficult to observe in other animal models. 36,37 A mutant zebrafish lacking PSEN1 has been used to study the histaminergic neural system of the brain, which is essential in mediating the cognitive functions affected in AD. Analysis of histamine neuron numbers in the PSEN1 −/− zebrafish brain revealed that PSEN1 is a regulator of histaminergic neuronal development.…”