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Changes in the brain and plasma Aβ peptide levels with age and its relationship with cognitive impairment in the APPswe/PS1dE9 mouse model of Alzheimer's disease.
Neuroscience. 2014 Mar 28; 263:269-79.N

Abstract

Double transgenic mice expressing mutant amyloid precursor protein (APPswe) and mutant presenilin 1 (PS1dE9) are a model of Alzheimer-type amyloidosis and are widely used in experimental studies. In the present work, the relationships between brain and plasma amyloid-β peptide (Aβ) levels and cognitive impairments were examined in male APPswe/PS1dE9 double transgenic mice at different ages. When compared with non-transgenic littermates, APPswe/PS1dE9 mice exhibited significant learning deficits from the age of 6months (M6), which were aggravated at later stages of life (M8 and M12). Sporadic brain amyloid plaques were observed in mice as early as M3 and progressively increased in number and size up to M12. A similar increase was observed in brain insoluble Aβ levels as assessed by enzyme-linked immunosorbent assay (ELISA). In particular, the levels of brain insoluble Aβ peptides rose steeply from M4 to M6. Interestingly, this pronounced amyloid deposition was accompanied by a temporary fall in the concentration of brain soluble and membrane-bound Aβ peptides at M6 that rose again at M8 and M12. The plasma levels of Aβ40 and Aβ42 decreased with advancing age up to M8, when they stabilized at M12. This decrease in plasma Aβ levels coincided with the observed increase in insoluble brain Aβ levels. These results could be useful for developing plasma Aβ levels as possible biomarkers of the cerebral amyloidosis and provide advances in the knowledge of the Aβ peptide biochemical changes that occur in the brain of Alzheimer's disease patients.

Authors+Show Affiliations

Araclon Biotech, I+D Laboratory, Vía Hispanidad 21, 50009 Zaragoza, Spain. Electronic address: mizco@araclon.com.Department of Physiology and Pharmacology, Faculty of Medicine, Cardenal Herrera Oria s/n, 39011 Santander, Spain. Electronic address: paula.martinezf@unican.es.Department of Physiology and Pharmacology, Faculty of Medicine, Cardenal Herrera Oria s/n, 39011 Santander, Spain. Electronic address: andreacorrales77@gmail.com.Araclon Biotech, I+D Laboratory, Vía Hispanidad 21, 50009 Zaragoza, Spain. Electronic address: nfandos@araclon.com.Department of Physiology and Pharmacology, Faculty of Medicine, Cardenal Herrera Oria s/n, 39011 Santander, Spain. Electronic address: susanagace@gmail.com.Araclon Biotech, I+D Laboratory, Vía Hispanidad 21, 50009 Zaragoza, Spain. Electronic address: dinsua@araclon.com.Araclon Biotech, I+D Laboratory, Vía Hispanidad 21, 50009 Zaragoza, Spain. Electronic address: mmontanes@araclon.com.Araclon Biotech, I+D Laboratory, Vía Hispanidad 21, 50009 Zaragoza, Spain. Electronic address: vperez@araclon.com.Department of Physiology and Pharmacology, Faculty of Medicine, Cardenal Herrera Oria s/n, 39011 Santander, Spain. Electronic address: ruedan@unican.es.Department of Physiology and Pharmacology, Faculty of Medicine, Cardenal Herrera Oria s/n, 39011 Santander, Spain. Electronic address: vidalv@unican.es.Department of Physiology and Pharmacology, Faculty of Medicine, Cardenal Herrera Oria s/n, 39011 Santander, Spain. Electronic address: martinec@unican.es.Araclon Biotech, I+D Laboratory, Vía Hispanidad 21, 50009 Zaragoza, Spain. Electronic address: ppesini@araclon.com.Araclon Biotech, I+D Laboratory, Vía Hispanidad 21, 50009 Zaragoza, Spain. Electronic address: msarasa@araclon.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24447596

Citation

Izco, M, et al. "Changes in the Brain and Plasma Aβ Peptide Levels With Age and Its Relationship With Cognitive Impairment in the APPswe/PS1dE9 Mouse Model of Alzheimer's Disease." Neuroscience, vol. 263, 2014, pp. 269-79.
Izco M, Martínez P, Corrales A, et al. Changes in the brain and plasma Aβ peptide levels with age and its relationship with cognitive impairment in the APPswe/PS1dE9 mouse model of Alzheimer's disease. Neuroscience. 2014;263:269-79.
Izco, M., Martínez, P., Corrales, A., Fandos, N., García, S., Insua, D., Montañes, M., Pérez-Grijalba, V., Rueda, N., Vidal, V., Martínez-Cué, C., Pesini, P., & Sarasa, M. (2014). Changes in the brain and plasma Aβ peptide levels with age and its relationship with cognitive impairment in the APPswe/PS1dE9 mouse model of Alzheimer's disease. Neuroscience, 263, 269-79. https://doi.org/10.1016/j.neuroscience.2014.01.003
Izco M, et al. Changes in the Brain and Plasma Aβ Peptide Levels With Age and Its Relationship With Cognitive Impairment in the APPswe/PS1dE9 Mouse Model of Alzheimer's Disease. Neuroscience. 2014 Mar 28;263:269-79. PubMed PMID: 24447596.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Changes in the brain and plasma Aβ peptide levels with age and its relationship with cognitive impairment in the APPswe/PS1dE9 mouse model of Alzheimer's disease. AU - Izco,M, AU - Martínez,P, AU - Corrales,A, AU - Fandos,N, AU - García,S, AU - Insua,D, AU - Montañes,M, AU - Pérez-Grijalba,V, AU - Rueda,N, AU - Vidal,V, AU - Martínez-Cué,C, AU - Pesini,P, AU - Sarasa,M, Y1 - 2014/01/18/ PY - 2013/09/25/received PY - 2013/12/11/revised PY - 2014/01/02/accepted PY - 2014/1/23/entrez PY - 2014/1/23/pubmed PY - 2014/11/2/medline KW - APPswe/PS1dE9 transgenic animal model KW - Alzheimer’s disease KW - brain Aβ levels KW - memory deficits KW - plasma Aβ levels KW - β-amyloid peptides SP - 269 EP - 79 JF - Neuroscience JO - Neuroscience VL - 263 N2 - Double transgenic mice expressing mutant amyloid precursor protein (APPswe) and mutant presenilin 1 (PS1dE9) are a model of Alzheimer-type amyloidosis and are widely used in experimental studies. In the present work, the relationships between brain and plasma amyloid-β peptide (Aβ) levels and cognitive impairments were examined in male APPswe/PS1dE9 double transgenic mice at different ages. When compared with non-transgenic littermates, APPswe/PS1dE9 mice exhibited significant learning deficits from the age of 6months (M6), which were aggravated at later stages of life (M8 and M12). Sporadic brain amyloid plaques were observed in mice as early as M3 and progressively increased in number and size up to M12. A similar increase was observed in brain insoluble Aβ levels as assessed by enzyme-linked immunosorbent assay (ELISA). In particular, the levels of brain insoluble Aβ peptides rose steeply from M4 to M6. Interestingly, this pronounced amyloid deposition was accompanied by a temporary fall in the concentration of brain soluble and membrane-bound Aβ peptides at M6 that rose again at M8 and M12. The plasma levels of Aβ40 and Aβ42 decreased with advancing age up to M8, when they stabilized at M12. This decrease in plasma Aβ levels coincided with the observed increase in insoluble brain Aβ levels. These results could be useful for developing plasma Aβ levels as possible biomarkers of the cerebral amyloidosis and provide advances in the knowledge of the Aβ peptide biochemical changes that occur in the brain of Alzheimer's disease patients. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/24447596/Changes_in_the_brain_and_plasma_Aβ_peptide_levels_with_age_and_its_relationship_with_cognitive_impairment_in_the_APPswe/PS1dE9_mouse_model_of_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(14)00007-4 DB - PRIME DP - Unbound Medicine ER -