Genotype load modulates amyloid burden and anxiety-like patterns in male 3xTg-AD survivors despite similar neuro-immunoendocrine, synaptic and cognitive impairments
Muntsant, Aida (Universitat Autònoma de Barcelona. Institut de Neurociències)
Gimenez-Llort, Lydia (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)

Fecha:	2021
Resumen:	The wide heterogeneity and complexity of Alzheimer's disease (AD) patients' clinical profiles and increased mortality highlight the relevance of personalized-based interventions and the need for end-of-life/survival predictors. At the translational level, studying genetic and age interactions in a context of different levels of expression of AD-genetic-load can help to understand this heterogeneity better. In the present report, a singular cohort of long-lived (19-month-old survivors) heterozygous and homozygous male 3xTg-AD mice were studied to determine whether their AD-genotype load can modulate the brain and peripheral pathological burden, behavioral phenotypes, and neuro-immunoendocrine status, compared to age-matched non-transgenic controls. The results indicated increased amyloid precursor protein (APP) levels in a genetic-load-dependent manner but convergent synaptophysin and choline acetyltransferase brain levels. Cognitive impairment and HPA-axis hyperactivation were salient traits in both 3xTg-AD survivor groups. In contrast, genetic load elicited different anxiety-like profiles, with hypoactive homozygous, while heterozygous resembled controls in some traits and risk assessment. Complex neuro-immunoendocrine crosstalk was also observed. Bodyweight loss and splenic, renal, and hepatic histopathological injury scores provided evidence of the systemic features of AD, despite similar peripheral organs' oxidative stress. The present study provides an interesting translational scenario to study further genetic-load and age-dependent vulnerability/compensatory mechanisms in Alzheimer's disease.
Ayudas:	European Commission. Horizon 2020 737390
Nota:	Altres ajuts: UAB-GE-260408
Derechos:	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.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Alzheimer's disease ; Genetic load ; Survival ; End-of-life ; Frailty ; Heterogeneity ; BPSD ; NPS ; Neuro-immunoendocrine crosstalk
Publicado en:	Biomedicines, Vol. 9 (2021) , ISSN 2227-9059

DOI: 10.3390/biomedicines9070715
PMID: 34201608

26 p, 8.8 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut de Neurociències (INc)
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