Saito et al developed a novel amyloid precursor protein (APP) knock-in mouse model (APP) for Alzheimer's disease (AD) to overcome the problem of overexpression of APP in available transgenic mouse models. However, this new mouse model for AD is not fully characterized age-dependently with respect to behavioral and biochemical changes. Therefore, in the present study, we performed an age-dependent behavioral and biochemical characterization of this newly developed mouse model. Here, we used 3-, 6-, 9-, and 12-month-old APPand C57BL/6J mice. We used a separate cohort of animals at each age point. Morris water maze, object recognition, and fear-conditioning tests were used for the assessment of learning and memory functions and open-field test to measure the general locomotor activity of mice. After each testing point, we perfused the mice and collected the brain for immunostaining. We performed the immunostaining for amyloid burden (4G8), glial fibrillary acidic protein, choline acetyltransferase, and tyrosine hydroxylase. The results of the present study indicate that APPmice showed age-dependent memory impairments with maximum impairment at the age of 12 months. These mice showed memory impairment in Morris water maze and fear conditioning tests when they were 6 months old, whereas, in object recognition test, memory deficit was found in 9-month-old mice. APPmice age dependently showed an increase in amyloid load in different brain regions. However, no amyloid pathology was found in 3-month-old APPmice. Choline acetyltransferase neurons in medial septum-diagonal band complex and tyrosine hydroxylase neurons in locus coeruleus were decreased significantly in APPmice. This mouse model also indicated an age-dependent increase in glial fibrillary acidic protein load. It can be concluded from the results that the APPmouse model may be used to explore the Aβ hypothesis, molecular, and cellular mechanisms involved in AD pathology and to screen the therapeutic potential compounds for the treatment of AD. NL-G-F NL-G-F NL-G-F NL-G-F NL-G-F NL-G-F NL-G-F
