Profiling the human hippocampal proteome at all pathologic stages of Alzheimer's disease

Alzheimers Dement. 2016 Jun;12(6):654-68. doi: 10.1016/j.jalz.2015.11.002. Epub 2016 Jan 6.


Introduction: 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).

Methods: 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.

Results: 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.

Discussion: 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.

Keywords: Alzheimer's disease; Hippocampus; Human; Laser dissection; Proteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / pathology*
  • CA1 Region, Hippocampal / metabolism*
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Humans
  • Laser Capture Microdissection
  • Male
  • Mass Spectrometry
  • Middle Aged
  • Nerve Tissue Proteins / metabolism
  • Proteome / metabolism*
  • Proteomics
  • Psychiatric Status Rating Scales
  • Signal Transduction


  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Proteome