Survival Curves and Behavioral Profiles of Female 3xTg-AD Mice Surviving to 18-Months of Age as Compared to Mice with Normal Aging

Abstract

New evidence reveals a high degree of heterogeneity in Alzheimer’s disease (AD) clinical and temporal patterns, supporting the existence of several subgroups of patients. Prognosticators of end-of-life dementia specific to elderly patients are necessary to address this heterogeneity. Among 3xTg-AD mice, a widely-used model for AD, a very small number of animals overcome advanced neuropathological stages of disease beyond 18 months of age. They are usually females, which reach longevity in spite of worse neuropathological status as compared to males (the morbidity/mortality paradox). We posit that 3xTg-AD long-term survivors could serve to model end-of-life dementia but also aware about the mortality selection bias. In the present study, we performed behavioral and functional phenotype in long-term survivors, 18-month-old female 3xTg-AD mice and age-matched wildtype undergoing normal aging. Animals were followed up until natural death to correlate survival with phenotype assessments. Strong similarity of their behavioral profiles in all the variables analyzed (e.g. reflexes, sensorimotor functions, locomotion, exploration, emotionality, and anxiety-like behaviors) was found, with the exception of memory impairment, which was a salient trait in old 3xTg-AD survivors. The two groups showed similar mean life expectancy and had behavioral correlates among lifespan, neophobia and long-term memory in common, with some distinctions in 3xTg-AD, supporting recent studies in end-of-life patients. In spite of the small sample size, this brief report presents an interesting scenario to further study heterogeneity and survival in Alzheimer’s disease. 3xTg-AD survivors may be a model to gain insight into the frailty/survival paradigm in normal and pathological aging.

Impact of Chronic Risperidone Use on Behavior and Survival of 3xTg-AD Mice Model of Alzheimer’s Disease and Mice With Normal Aging

“…The crosstalk refers to the oxi-inflamaging theory developed in PAM and NPAM mice where the divergence of the speed of the aging process (premature in PAM and normal in NPAM) was correlated with immune function, oxidative stress, and worse/better copying with stress strategies in the TM (Guayerbas et al, 2001). While neophobia and worse long-term memory were found to be correlated with reduced survival in female NTg and 3xTg-AD mice (Torres-Lista et al, 2017), it was surprising that memory variables did not correlate with survival in the present work, probably due to the mortality bias, as discussed above. Thus, this was probably because the impairment was less pronounced in the current male sample, as correlation was only found with the level of optimization of the performance (day 4) in the water maze.…”

Long-term Treatment with Low-Dose Caffeine Worsens BPSD-Like Profile in 3xTg-AD Mice Model of Alzheimer’s Disease and Affects Mice with Normal Aging

“…The behavioral effects were assessed at advanced stages (13 month of age) when both amyloid and tau pathologies are present ( Oddo et al, 2003 ). At this age, we have consistently reported that survival male 3xTg-AD mice starts to be compromised ( Giménez-Llort et al, 2008 , 2010 ; García-Mesa et al, 2016 ; Torres-Lista et al, 2017 ). Effects were compared to age-matched NTg mice with normal aging, that according to the background strain represent overcoming the middle age.…”

Impact of Social Isolation on the Behavioral, Functional Profiles, and Hippocampal Atrophy Asymmetry in Dementia in Times of Coronavirus Pandemic (COVID-19): A Translational Neuroscience Approach

“…In this other test, which did not reach statistical significance, the subsequent analysis of the long-term habituation in the activity cages showed a worse (lower) pattern in the 3xTg-AD mice. Our laboratory has previously described the convergence of profiles in the context of poor aging and related physical and cognitive declines in NTg mice as part of the complexity of age-related scenarios and heterogeneity among all populations, including wild-type mice (not just 3xTg-AD mice) ( 69 ). Interestingly, these smooth patterns in middle-aged mice housed in standard conditions also emphasized the impact of isolation shown as prominent levels of both horizontal and vertical activities.…”