Age-related neuropsychiatric symptoms in presenilins conditional double knockout mice

Alzheimer's disease (AD) is the most common form of dementia and causes impairments of memory, cognition and behavior. Remarkably, most AD patients exhibit personality changes that often precede other early clinical manifestations. Conditional presenilin1 (PS1) and presenilin2 (PS2) double knockout (DKO) mice have age-related forebrain atrophy, tau hyperphosphorylation, synaptic dysfunction, cognitive deficits and increased inflammatory responses in both the periphery and the brain. Whether these mice have age-related emotional changes have not yet been investigated. In the present study, we used 2-, 6- and 11-month-old DKO and littermate control (CON) mice to examine their age-related emotional conditions. Our results indicate that DKO mice have observable age-related neuropsychiatric symptoms, such as anxiety, irritability, depression, apathy, aggressivity, anhedonia and aberrant motor behavior when compared with other AD-like mouse models. In summary, our results not only indicate that DKO mice may be a valuable model for probing age-related AD diagnoses but also suggest a new pathogenesis of neurodegenerative diseases that is worth further investigation.