Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 54, Issue 4, Pages 1671-1686Publisher
IOS PRESS
DOI: 10.3233/JAD-160271
Keywords
Alzheimer's disease; endocytosis; exocytosis; exosomes; extracellular vesicles; immobilized/chemistry antibodies; mass spectrometry
Categories
Funding
- Uppsala Berzelii Technology Centre for Neurodiagnostics
- Swedish Governmental Agency for Innovation Systems
- Alzheimer fonden
- Gun och Bertil Stohnes stiftelse
- Lars Hiertas Minne stiftelse
- Swedish Research Council [P29797-1, 621-2011-4423]
- ProNova VINN Excellence Centre for Protein Technology (VINNOVA, Swedish Governmental Agency for Innovation Systems)
- Knut and Alice Wallenberg Foundation
- Geriatriska fonden
- KTH Center for Applied Proteomics - Erling-Persson Family Foundation
- SciLifeLab
- stiftelsen for Gamla Tjanarinnor
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Background: Alzheimer's disease (AD) is a chronic neurodegenerative disorder accounting for more than 50% of all dementia cases. AD neuropathology is characterized by the formation of extracellular plaques and intracellular neurofibrillary tangles consisting of aggregated amyloid-beta and tau, respectively. The disease mechanism has only been partially elucidated and is believed to also involve many other proteins. Objective: This study intended to perform a proteomic profiling of post mortem AD brains and compare it with control brains as well as brains from other neurological diseases to gain insight into the disease pathology. Methods: Here we used label-free shotgun mass spectrometry to analyze temporal neocortex samples from AD, other neurological disorders, and non-demented controls, in order to identify additional proteins that are altered in AD. The mass spectrometry results were verified by antibody suspension bead arrays. Results: We found 50 proteins with altered levels between AD and control brains. The majority of these proteins were found at lower levels in AD. Pathway analyses revealed that several of the decreased proteins play a role in exocytic and endocytic pathways, whereas several of the increased proteins are related to extracellular vesicles. Using antibody-based analysis, we verified the mass spectrometry results for five representative proteins from this group of proteins (CD9, HSP72, PI42A, TALDO, and VAMP2) and GFAP, a marker for neuroinflammation. Conclusions: Several proteins involved in exo-endocytic pathways and extracellular vesicle functions display altered levels in the AD brain. We hypothesize that such changes may result in disturbed cellular clearance and a perturbed cell-to-cell communication that may contribute to neuronal dysfunction and cell death in AD.
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