%0 Journal Article
%T Intracellular distribution of amyloid beta peptide and its relationship to the lysosomal system
%A Zheng Lin
%A Cedazo-Minguez Angel
%A Hallbeck Martin
%A Jerhammar Fredrik
%J Translational Neurodegeneration
%D 2012
%I BioMed Central
%R 10.1186/2047-9158-1-19
%X Background Amyloid beta peptide (A¦Â) is the main component of extraneuronal senile plaques typical of Alzheimer¡¯s disease (AD) brains. Although A¦Â is produced by normal neurons, it is shown to accumulate in large amounts within neuronal lysosomes in AD. We have recently shown that under normal conditions the majority of A¦Â is localized extralysosomally, while oxidative stress significantly increases intralysosomal A¦Â content through activation of macroautophagy. It is also suggested that impaired A¦Â secretion and resulting intraneuronal increase of A¦Â can contribute to AD pathology. However, it is not clear how A¦Â is distributed inside normal neurons, and how this distribution is effected when A¦Â secretion is inhibited. Methods Using retinoic acid differentiated neuroblastoma cells and neonatal rat cortical neurons, we studied intracellular distribution of A¦Â by double immunofluorescence microscopy for A¦Â40 or A¦Â42 and different organelle markers. In addition, we analysed the effect of tetanus toxin-induced exocytosis inhibition on the intracellular distribution of A¦Â. Results Under normal conditions, A¦Â was found in the small cytoplasmic granules in both neurites and perikarya. Only minor portion of A¦Â was colocalized with trans-Golgi network, Golgi-derived vesicles, early and late endosomes, lysosomes, and synaptic vesicles, while the majority of A¦Â granules were not colocalized with any of these structures. Furthermore, treatment of cells with tetanus toxin significantly increased the amount of intracellular A¦Â in both perikarya and neurites. Finally, we found that tetanus toxin increased the levels of intralysosomal A¦Â although the majority of A¦Â still remained extralysosomally. Conclusion Our results indicate that most A¦Â is not localized to Golgi-related structures, endosomes, lysosomes secretory vesicles or other organelles, while the suppression of A¦Â secretion increases intracellular intra- and extralysosomal A¦Â.
%K Alzheimer disease
%K Amyloid ¦Â-protein
%K Colocalization
%K Exocytosis
%K Immunocytochemistry
%K Lysosomes
%U http://www.translationalneurodegeneration.com/content/1/1/19