Survival Bias and Crosstalk between Chronological and Behavioral Age : Age- and Genotype-Sensitivity Tests Define Behavioral Signatures in Middle-Aged, Old, and Long-Lived Mice with Normal and AD-Associated Aging
Gimenez-Llort, Lydia (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Marín-Pardo, Daniela (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Marazuela, Paula (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Hernandez Guillamon, Maria Mar (Hospital Universitari Vall d'Hebron. Institut de Recerca)

Date:	2021
Abstract:	New evidence refers to a high degree of heterogeneity in normal but also Alzheimer's disease (AD) clinical and temporal patterns, increased mortality, and the need to find specific end-of-life prognosticators. This heterogeneity is scarcely explored in very old male AD mice models due to their reduced survival. In the present work, using 915 (432 APP23 and 483 C57BL/6 littermates) mice, we confirmed the better survival curves in male than female APP23 mice and respective wildtypes, providing the chance to characterize behavioral signatures in middle-aged, old, and long-lived male animals. The sensitivity of a battery of seven paradigms for comprehensive screening of motor (activity and gait analysis), neuropsychiatric and cognitive symptoms was analyzed using a cohort of 56 animals, composed of 12-, 18- and 24-month-old male APP23 mice and wildtype littermates. Most variables analyzed detected age-related differences. However, variables related to coping with stress, thigmotaxis, frailty, gait, and poor cognition better discriminated the behavioral phenotype of male APP23 mice through the three old ages compared with controls. Most importantly, non-linear age- and genotype-dependent behavioral signatures were found in long-lived animals, suggesting crosstalk between chronological and biological/behavioral ages useful to study underlying mechanisms and distinct compensations through physiological and AD-associated aging.
Grants:	Instituto de Salud Carlos III RD16/0019/0021
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Survival ; Aging ; Alzheimer's disease ; Heterogeneity ; Long-life ; Gait analysis ; Cognition ; BPSD
Published in:	Biomedicines, Vol. 9 (june 2021) , ISSN 2227-9059

DOI: 10.3390/biomedicines9060636
PMID: 34199476

22 p, 3.2 MB

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