Torres-Lista Virginia, De la Fuente Mónica, Giménez-Llort Lydia
Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, Spain.
Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
J Alzheimers Dis Rep. 2017 Jul 6;1(1):47-57. doi: 10.3233/ADR-170011.
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.
新证据揭示了阿尔茨海默病（AD）临床和时间模式的高度异质性，支持了存在几个患者亚组的观点。针对老年患者的临终痴呆预后指标对于解决这种异质性是必要的。在3xTg-AD小鼠（一种广泛使用的AD模型）中，极少数动物能克服超过18个月龄的疾病晚期神经病理阶段。它们通常是雌性，尽管与雄性相比神经病理状态更差，但仍能达到长寿（发病率/死亡率悖论）。我们认为3xTg-AD长期存活者可用于模拟临终痴呆，但也要意识到死亡率选择偏差。在本研究中，我们对长期存活者、18月龄雌性3xTg-AD小鼠和年龄匹配的正常衰老野生型小鼠进行了行为和功能表型分析。对动物进行随访直至自然死亡，以将存活情况与表型评估相关联。在分析的所有变量（如反射、感觉运动功能、运动、探索、情绪和焦虑样行为）中，发现它们的行为特征有很强的相似性，但记忆障碍除外，这是老年3xTg-AD存活者的一个显著特征。两组的平均预期寿命相似，在寿命、新事物恐惧和长期记忆方面有共同的行为关联，3xTg-AD组有一些差异，这支持了最近对临终患者的研究。尽管样本量较小，但这份简短报告呈现了一个有趣的场景，可进一步研究阿尔茨海默病的异质性和存活情况。3xTg-AD存活者可能是一个模型，有助于深入了解正常和病理性衰老中的虚弱/存活模式。
