Format

Send to

Choose Destination
Biochim Biophys Acta. 2015 Jul;1853(7):1646-57. doi: 10.1016/j.bbamcr.2015.03.003. Epub 2015 Mar 17.

mTor mediates tau localization and secretion: Implication for Alzheimer's disease.

Author information

1
Karolinska Institutet, NVS Department, Centrum for Alzheimer Research, Division for Neurogeriatrics, Novum, SE 14186 Stockholm, Sweden; Department of Clinical Laboratory, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China.
2
Karolinska Institutet, NVS Department, Centrum for Alzheimer Research, Division for Neurogeriatrics, Novum, SE 14186 Stockholm, Sweden.
3
Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, SE 141 86 Stockholm, Sweden.
4
Karolinska Institutet, NVS Department, Centrum for Alzheimer Research, Division for Neurogeriatrics, Novum, SE 14186 Stockholm, Sweden; Department of Pathology, Guiyang Medical College, Guiyang 550004, Guizhou, China; Molecular Biology, Guiyang Medical College, Guiyang 550004, Guizhou, China.
5
Karolinska Institutet, NVS Department, Centrum for Alzheimer Research, Division for Neurogeriatrics, Novum, SE 14186 Stockholm, Sweden; Department of Neurology, Xuan Wu Hospital, Capital Medical University, China; Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing 100053, China. Electronic address: Jin-Jing.Pei@ki.se.

Abstract

Abnormally hyperphosphorylated tau aggregates form paired helical filaments (PHFs) in neurofibrillary tangles, a key hallmark of Alzheimer's disease (AD) and other tauopathies. The cerebrospinal fluid (CSF) levels of soluble total tau and phospho-tau from clinically diagnosed AD patients are significantly higher compared with controls. Data from both in vitro and in vivo AD models have implied that an aberrant increase of mammalian target of rapamycin (mTor) signaling may be a causative factor for the formation of abnormally hyperphosphorylated tau. In the present study, we showed that in post-mortem human AD brain, tau was localized within different organelles (autophagic vacuoles, endoplasmic reticulum, Golgi complexes, and mitochondria). In human SH-SY5Y neuroblastoma cells stably carrying different genetic variants of mTor, we found a common link between the synthesis and distribution of intracellular tau. mTor overexpression or the lack of its expression was responsible for the altered balance of phosphorylated (p-)/-non phosphorylated (Np-) tau in the cytoplasm and different cellular compartments, which might facilitate tau deposition. Up-regulated mTor activity resulted in a significant increase in the amount of cytosolic tau as well as its re-localization to exocytotic vesicles that were not associated with exosomes. These results have implicated that mTor is involved in regulating tau distribution in subcellular organelles and in the initiation of tau secretion from cells to extracellular space.

KEYWORDS:

Alzheimer's disease; Autophagy; Tau phosphorylation; Tau secretion; mTor

PMID:
25791428
DOI:
10.1016/j.bbamcr.2015.03.003
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center