Presenilin PS1∆E9 disrupts mobility of secretory organelles in rat astrocytes

Aim Alzheimer's disease (AD) is largely considered a neuron‐derived insult, but also involves failure of astroglia. A recent study indicated that mutated presenilin 1 (PS1M146V), a putative endoplasmic reticulum (ER) Ca2+ channel with decreased Ca2+ conductance, impairs the traffic of astroglial peptidergic vesicles. Whether other pathogenically relevant PS1 mutants, such as PS1ΔE9, which code for ER channel with putative increased Ca2+ conductance, similarly affect vesicle traffic, is unknown. Methods Here, we cotransfected rat astrocytes with plasmids encoding mutant PS1ΔE9 and atrial natriuretic peptide or vesicular glutamate transporter 1 tagged with fluorescent proteins (pANP.emd or pVGLUT1‐EGFP respectively), to microscopically examine whether alterations in vesicle mobility and Ca2+‐regulated release of gliosignalling molecules manifest as a general vesicle‐based defect; control cells were transfected to co‐express exogenous or native wild‐type PS1 and pANP.emd or pVGLUT1‐EGFP. The vesicle mobility was analysed at rest and after ATP stimulation that increased intracellular calcium activity. Results In PS1ΔE9 astrocytes, spontaneous mobility of both vesicle types was reduced (P