Anxiety is a Risk Factor of AD at an Early Stage With Gender Differences in APP V717I Transgenic Mice

Objective Alzheimer's disease (AD) is the most common form of dementia. There are two main risk factors for developing AD-age and gender. By aging, preclinical and clinical symptoms are emerging in succession. Anxiety is one of the typical early symptoms during AD processing. Besides, the incidence of AD is higher in women than in men. However, although the differences were observed in the AD cohort, there is a lack of the assessment of AD experimental animal models within age and gender. Methods We choose the APP London mutation (Val717Ile) transgenic (Tg) mice for study. This is one of the first described mutations in APP, with the early onset of AD. To illustrate if the gender difference occurred in APP V717I mice during AD processing, we made use of animal behavior tests, such as open field test, step-down test and Morris water maze to evaluate the noncognitive symptom and cognitive symptom. Results In this study, we found that at 6-month age, female Tg mice showed significant anxiety, while male Tg mice only showed anxiety at 10-month age. At 6-month age, both male and female Tg mice did not show cognitive deficits; but, at 10-month age, both genders showed significant cognitive impairments. Conclusion These results indicated that APP V717I Tg mice showed anxiety-like activity before the occurrence of memory deficits; in the process of AD, APP V717I Tg mice have a clear difference in age and gender. This study provides favorable evidence for age and gender differences in the process of AD. The mouse model is also expected to become an essential tool for AD drug research, aiming to help precision medicine and distinguish gender differences in drug use.

Automated summary

This study aimed to investigate the age and gender differences in APP V717I transgenic mice during the progression of Alzheimer's disease (AD). The results showed that female mice exhibited significant anxiety at 6 months of age, while male mice only showed anxiety at 10 months. Both genders displayed cognitive impairments at 10 months but not at 6 months. These findings suggest that there are distinct age and gender differences in AD progression, and the APP V717I mouse model could serve as a valuable tool for AD research and precision medicine.