title: Profiling the human hippocampal proteome at all pathologic stages of Alzheimer's disease.
abstract: We performed a comprehensive quantitative proteomics study on human hippocampus tissue involving all Braak stages to assess changes in protein abundance over the various stages of Alzheimer's disease (AD).
  
  
  
  Hippocampal subareas CA1 and subiculum of 40 cases were isolated using laser capture microdissection and analyzed using mass spectrometry. Immunoblotting and immunohistochemistry were used for validation.
  
  
  
  Over the Braak stages, an altered expression was found for 372 proteins including changes in levels of extracellular matrix components, and in calcium-dependent signaling proteins. Early changes were observed in levels of proteins related to cytoskeletal dynamics and synaptic components including an increase in RIMS1 and GRIK4. Several synaptic proteins, such as BSN, LIN7A, DLG2, -3, and -4, exhibit an early-up, late-down expression pattern.
  
  
  
  This study provides new insight into AD-dependent changes in protein levels in the hippocampus during AD pathology, identifying potential novel therapeutic targets and biomarkers.
authors.affiliation: Department of Pathology, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands; Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: David C
authors.initials: DC
authors.lastname: Hondius
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Pim
authors.initials: P
authors.lastname: van Nierop
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Ka Wan
authors.initials: KW
authors.lastname: Li
authors.affiliation: Department of Pathology, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jeroen J M
authors.initials: JJ
authors.lastname: Hoozemans
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Roel C
authors.initials: RC
authors.lastname: van der Schors
authors.affiliation: Department of Pathology, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors.forename: Elise S
authors.initials: ES
authors.lastname: van Haastert
authors.affiliation: Department of Pathology, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors.forename: Saskia M
authors.initials: SM
authors.lastname: van der Vies
authors.affiliation: Department of Pathology, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.
authors.forename: Annemieke J M
authors.initials: AJ
authors.lastname: Rozemuller
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, Amsterdam, The Netherlands. Electronic address: a.b.smit@vu.nl.
authors.forename: August B
authors.initials: AB
authors.lastname: Smit
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D056547:CA1 Region, Hippocampal / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D061346:Laser Capture Microdissection; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D011569:Psychiatric Status Rating Scales; D015398:Signal Transduction
chemical_list: D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D020543:Proteome
keywords: Alzheimer's disease; Hippocampus; Human; Laser dissection; Proteomics