Plasma Levels of tPA and Aging: A Molecular Detective Story

Published on June 8, 2022

Scientists have embarked on a thrilling molecular detective story to uncover the mysterious relationship between plasma levels of tissue-type plasminogen activator (tPA) and aging, particularly in the context of Alzheimer’s disease. Like a determined investigator, they examined the links between tPA plasma concentration and cognition, brain structure, brain function, and amyloid burden in a diverse group of participants. This investigation revealed that as age increases, so does the concentration of tPA in the blood, with males having higher levels than females. Interestingly, among cognitively unimpaired adults and individuals with Alzheimer’s disease, tPA did not differ significantly. However, in cognitively unimpaired adults, higher tPA levels were associated with reduced global brain volume. Surprisingly, no connection was found between tPA levels and brain metabolism or amyloid deposition. Instead, tPA changes seemed linked to alterations in blood pressure, glycemia, and body mass index. While these findings shed light on the complex relationship between tPA and aging-related neuronal alterations, there is still much to unravel about this fascinating molecular protagonist! Dive into the original research for a deeper understanding.

Tissue-type plasminogen activator (tPA) is a protease known for its fibrinolytic action but is also involved in physiological and pathophysiological aging processes; including amyloid elimination and synaptic plasticity. The aim of the study was to investigate the role of tPA in cognitive and brain aging. Therefore, we assessed the links between tPA plasma concentration and cognition, structural MRI, FDG-PET and Flobetapir-PET neuroimaging in 155 cognitively unimpaired adults (CUA, aged 20-85 years old) and 32 patients with Alzheimer’s disease (ALZ). A positive correlation was found between tPA and age in CUA (p < 0.001), with males showing higher tPA than females (p = 0.05). No significant difference was found between ALZ patients and cognitively unimpaired elders (CUE). Plasma tPA in CUA negatively correlated with global brain volume. No correlation was found with brain FDG metabolism or amyloid deposition. Age-related tPA changes were associated to changes in blood pressure, glycemia and body mass index. Within the ALZ patients, tPA didn’t correlate with any cognitive or neuroimaging measures, but only with physiological measures. Altogether our study suggests that increased tPA plasma concentration with age is related to neuronal alterations and cardiovascular risk factors.

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