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Investigation of annexin A5 as a biomarker for Alzheimer's disease using neuronal cell culture and mouse model
Author(s) -
Yamaguchi Mami,
Kokai Yasuo,
Imai ShinIchi,
Utsumi Kumiko,
Matsumoto Kyoichi,
Honda Hirohito,
Mizue Yuka,
Momma Masako,
Maeda Tetsu,
Toyomasu Shozo,
Ito Yoichi M.,
Kobayashi Seijyu,
Hashimoto Eri,
Saito Toshikazu,
Sohma Hitoshi
Publication year - 2010
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22427
Subject(s) - annexin , alzheimer's disease , annexin a1 , biology , microbiology and biotechnology , calcium metabolism , homeostasis , annexin a5 , cell culture , annexin a2 , calcium , endocrinology , medicine , chemistry , biochemistry , flow cytometry , disease , genetics
Alzheimer's disease (AD) differs from other forms of dementia in its relation to amyloid β peptide (Aβ). Aβ, a proteolytic product of amyloid precursor proteins (APP), has a toxic effect on neuronal cells, which involves perturbation of their Ca 2+ homeostasis. This effect implies that changes of protein expression in neuronal cells with calcium stress should provide a molecular marker for this disease. In the present study, we used the supernatant from a neuronal cell culture after incubation with or without Aβ and isolated a Ca 2+ ‐dependent acidic phospholipid binding fraction to perform a proteomic study. Several unique proteins were identified after incubation with Aβ. We focused on annexin A5, among these proteins, because it binds both Ca 2+ and lipids likely to be involved in calcium homeostasis. Tg2576 transgenic mice (AD model) overexpressing mutant human APP showed a significant increase of annexin A5 in the brain cortex but not in other organs, including liver, kidney, lung, and intestine. In human plasma samples, the level of annexin A5 was significantly increased in a proportion of AD patients compared with a control group ( P < 0.0001 in the logistic regression analysis). From the receiver operating characteristic (ROC) curve with plasma annexin A5 concentrations, the mean area under the curve (AUC 0.898) suggests that annexin A5 is a favorable marker for AD. © 2010 Wiley‐Liss, Inc.