title: Translational study of Alzheimer's disease (AD) biomarkers from brain tissues in AβPP/PS1 mice and serum of AD patients.
abstract: The aim of this study was to investigate potential biomarkers of Alzheimer's disease (AD). Changes in protein expression in brain tissues from AβPP/PS1 transgenic mice were evaluated using two-dimensional gel electrophoresis combined with LC-MS/MS. A total of 23 differentially expressed proteins were successfully identified in brain tissues of which 11 were validated by western blot. Then, the levels of these differentially expressed proteins in serum from AD patients and healthy controls were examined. Of these 11 proteins, levels of 5 changed in the same direction in the serum of AD patients as they did in mouse brain: cathepsin B, VDAC1, and cofilin-2 increased, and Alix and ACAP1 decreased. Alix, cofilin-2, and ACAP1 have not been previously associated with AD. More importantly, the serum levels of Alix, cofilin-2, and ACAP1 were significantly different between AD patients and healthy controls. Furthermore, the expressions of cathepsin B, cofilin-2, VDAC1, and ACAP1 strongly correlated with the Mini-Mental State Examination scores of the AD patients. The results indicate that these proteins are putative biomarkers of AD which may be useful in its diagnosis and in the evaluation of new anti-AD drugs both in pre-clinical and clinical studies.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Yingni
authors.initials: Y
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Xianfang
authors.initials: X
authors.lastname: Rong
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Shaofeng
authors.initials: S
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Wang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000235:genetics / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D001921:Brain / Q000473:pathology*; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D051379:Mice; D009154:Mutation / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics; D012044:Regression Analysis; D053719:Tandem Mass Spectrometry
chemical_list: D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; C508853:PSEN1 protein, human; D053764:Presenilin-1
keywords: Alzheimer's disease; biomarker; diagnosis; neurodegeneration; proteomics; serum; transgenic mice