title: Increased Levels of Extracellular Microvesicle Markers and Decreased Levels of Endocytic/Exocytic Proteins in the Alzheimer's Disease Brain.
abstract: 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-β and tau, respectively. The disease mechanism has only been partially elucidated and is believed to also involve many other proteins.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Analytical Chemistry, Department of Chemistry-BMC, Uppsala University, Uppsala, Sweden.
authors.forename: Sravani
authors.initials: S
authors.lastname: Musunuri
authors.affiliation: Department of Medical Sciences, Cancer Pharmacology and Computational Medicine, Uppsala University Academic Hospital, Uppsala, Sweden.
authors.forename: Payam Emami
authors.initials: PE
authors.lastname: Khoonsari
authors.affiliation: Affinity Proteomics, Science for Life Laboratory, School of Biotechnology, KTH Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Mikus
authors.affiliation: GE Healthcare Life Sciences, Uppsala, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Wetterhall
authors.affiliation: Department of Public Health/ Geriatrics, Uppsala University, Uppsala, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Häggmark-Mänberg
authors.affiliation: Department of Public Health/ Geriatrics, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Lannfelt
authors.affiliation: Department of Public Health/ Geriatrics, Uppsala University, Uppsala, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Erlandsson
authors.affiliation: Analytical Chemistry, Department of Chemistry-BMC, Uppsala University, Uppsala, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergquist
authors.affiliation: Department of Public Health/ Geriatrics, Uppsala University, Uppsala, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Ingelsson
authors.affiliation: Analytical Chemistry, Department of Chemistry-BMC, Uppsala University, Uppsala, Sweden.
authors.forename: Ganna
authors.initials: G
authors.lastname: Shevchenko
authors.affiliation: Affinity Proteomics, Science for Life Laboratory, School of Biotechnology, KTH Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Nilsson
authors.affiliation: Department of Medical Sciences, Cancer Pharmacology and Computational Medicine, Uppsala University Academic Hospital, Uppsala, Sweden.
authors.forename: Kim
authors.initials: K
authors.lastname: Kultima
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D055252:Cell-Derived Microparticles / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004705:Endocytosis / Q000502:physiology*; D005089:Exocytosis / Q000502:physiology*; D045604:Extracellular Fluid / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D060066:Protein Interaction Maps / Q000502:physiology; D022161:Transport Vesicles / Q000235:genetics / Q000378:metabolism
keywords: Alzheimer’s disease; chemistry antibodies; endocytosis; exocytosis; exosomes; extracellular vesicles; immobilized; mass spectrometry