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

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.

Keywords: APPswe/PS1dE9 transgenic animal model; Alzheimer’s disease; brain Aβ levels; memory deficits; plasma Aβ levels; β-amyloid peptides.