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Short-term modern life-like stress exacerbates Aβ-pathology and synapse loss in 3xTg-AD mice Baglietto-Vargas, David Chen, Yuncai Suh, Dongjin Ager, Rahasson Rodriguez-Ortiz, Carlos Medeiros, Rodrigo Myczek, Kristoffer Green, Kim N Baram, Tallie LaFerla, Frank Baglietto-Vargas, David Alzheimer, Enfermedad de Alzheimer's disease (AD) is a progressive neurological disorder that impairs memory and other cognitive functions in the elderly. The social and financial impacts of AD are overwhelming and are escalating exponentially as a result of population aging. Therefore, identifying AD-related risk factors and the development of more efficacious therapeutic approaches are critical to cure this neurological disorder. Current epidemiological evidence indicates that life experiences, including chronic stress, are a risk for AD. However, it is unknown if short-term stress, lasting for hours, influences the onset or progression of AD. Here, we determined the effect of short-term, multi-modal ‘modern life-like’ stress on AD pathogenesis and synaptic plasticity in mice bearing three AD mutations (the 3xTg-AD mouse model). We found that combined emotional and physical stress lasting 5 h severely impaired memory in wild-type mice and tended to impact it in already low-performing 3xTg-AD mice. This stress reduced the number of synapse-bearing dendritic spines in 3xTg-AD mice and increased Aβ levels by augmenting AβPP processing. Thus, short-term stress simulating modern-life conditions may exacerbate cognitive deficits in preclinical AD by accelerating amyloid pathology and reducing synapse numbers. 2025-01-16T12:26:43Z 2025-01-16T12:26:43Z 2015-09 journal article Baglietto-Vargas D, Chen Y, Suh D, Ager RR, Rodriguez-Ortiz CJ, Medeiros R, Myczek K, Green KN, Baram TZ, LaFerla FM. Short-term modern life-like stress exacerbates Aβ-pathology and synapse loss in 3xTg-AD mice. J Neurochem. 2015 Sep;134(5):915-26. doi: 10.1111/jnc.13195. Epub 2015 Jul 14. PMID: 26077803; PMCID: PMC4792118. https://hdl.handle.net/10630/36421 10.1111/jnc.13195. Epub 2015 Jul 14 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Wiley