Circulating plasminogen activator inhibitor‐1 (PAI‐1) levels in the preclinical stage of Alzheimer’s disease

Plasminogen activator inhibitor‐1 (PAI‐1), a secreted glycoprotein and member of the serine protease inhibitor family, has been implicated to have a role in Alzheimer’s disease (AD) pathogenesis by regulating amyloid‐beta (Aβ) accumulation (Neurobiol Aging 32:1079,2011; J Alzheimers Dis. 64:447,2018). A recent study found that plasma PAI‐1 was differentially expressed in subjects with Aβ pathology and neurodegeneration (A+TN+) compared to A‐TN‐ subjects, with decreased plasma PAI‐1 levels in clinical AD compared to cognitively normal controls (Alzheimers Dement 17:1452,2021). However, whether circulating PAI‐1 levels are altered during the preclinical stage of AD, where there is Aβ and tau pathology but no significant cognitive impairment, remains unclear.