Biology subjects

Mallone, A.

Publications and source records attributed to Mallone, A..

2 recordsLinked to original sources

bioRxiv2023

Early beta-amyloid accumulation in the brain is associated with peripheral T cell alterations

Fast and minimally invasive approaches for early, preclinical diagnosis of neurodegenerative Alzheimers disease (AD) are highly anticipated. Evidence of adaptive immune cells responding to cerebral {beta}-amyloidosis, one of the pathological hallmarks of AD, has raised the question of whether immune markers could be used as proxies for {beta}-amyloid accumulation in the brain. Here, we deploy multidimensional mass cytometry combined with unbiased machine learning techniques to immunophenotype peripheral blood mononuclear cells from study participants in cross-sectional and longitudinal cohorts. We show that increases in antigen-experienced adaptive immune cells in the blood, particularly CD45RA-reactivated T effector memory (TEMRA) cells, are associated with early accumulation of brain {beta}-amyloid and with changes in plasma AD biomarkers in still cognitively healthy subjects. Our results suggest that preclinical AD pathology is linked to systemic alterations of the adaptive immune system. These immunophenotype changes may help in the future to identify and develop novel diagnostic tools for early AD assessment and to better understand clinical outcomes.

immunology↗

bioRxiv2020

Human induced pluripotent stem cell-derived arteries as personalized models of atherosclerosis on-a-chip

Atherosclerosis is an arterial disease characterized by intravascular plaques. Disease hallmarks are vessel stenosis and hyperplasia, eventually escalating into plaque rupture and acute clinical presentations. Innate immune cells and local variations in hemodynamics are core players in the pathology, but their mutual relationship has never been investigated before due to the lack of modeling systems with adequate degree of complexity. Here, we combined computational fluid dynamics and tissue-engineering to achieve, for the first time in vitro, full atherosclerotic plaque development. Our model incorporates induced pluripotent stem cell-derived populations into small-caliber arteries that are cultured in atheroprone conditions. Using machine-learning-aided immunophenotyping, molecular and nanoprobe-based tensile analyses, we found that immune cells, extracellular matrix components and tensional state were comparable between in vitro and ex vivo human lesions. Our results provide further insights into the relation between hemodynamics and inflammation, introducing a versatile, scalable modeling tool to study atherosclerosis onset and progression.

bioengineering↗