TY - JOUR
T1 - Profiling the human hippocampal proteome at all pathologic stages of Alzheimer's disease
AU - Hondius, David C.
AU - Van Nierop, Pim
AU - Li, Ka Wan
AU - Hoozemans, Jeroen J.M.
AU - Van Der Schors, Roel C.
AU - Van Haastert, Elise S.
AU - Van Der Vies, Saskia M.
AU - Rozemuller, Annemieke J.M.
AU - Smit, August B.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Hippocampus
KW - Human
KW - Laser dissection
KW - Proteomics
UR - http://www.scopus.com/inward/record.url?scp=84973515259&partnerID=8YFLogxK
U2 - 10.1016/j.jalz.2015.11.002
DO - 10.1016/j.jalz.2015.11.002
M3 - Article
C2 - 26772638
AN - SCOPUS:84973515259
SN - 1552-5260
VL - 12
SP - 654
EP - 668
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 6
ER -