High circulating levels of midregional proenkephalin A predict vascular dementia: a population-based prospective study

Abstract

Midregional Pro-enkephalin A (MR-PENK A) and N-terminal Protachykinin A (NT-PTA) have been associated with vascular dementia. However, the longitudinal relationship between these biomarkers and incident dementia has not been fully investigated. in the population-based Malmö preventive Project, circulating levels of MR-PENK A and NT-PTA were determined in a random sample of 5,323 study participants (mean age: 69 ± 6 years) who were followed-up over a period of 4.6 ± 1.6 years. The study sample included 369 patients (7%) who were diagnosed in the same period with dementia. We analyzed relationship of MR-PENK A and NT-PTA with the risk of developing dementia by using multivariable-adjusted cox regression models adjusted for traditional risk factors. increased plasma levels of MR-PENK A were associated with higher risk of incident vascular dementia whereas no associations were found with all-cause or Alzheimer dementia. the risk of vascular dementia was mainly conferred by the highest quartile of MR-PENK as compared with lower quartiles. Elevated levels of NT-PTA yielded significant association with all-cause dementia or dementia subtypes. Elevated plasma concentration of MR-PENK A independently predicts vascular dementia in the general population. MR-PENK A may be used as an additional tool for identifying vascular subtype in ambiguous dementia cases.

Role of inflammatory markers in the diagnosis of vascular contributions to cognitive impairment and dementia: a systematic review and meta-analysis

“…The latter respond to the IL-6 stimuli by releasing chemokines and increasing the expression of cellular adhesion molecules as the intercellular adhesion molecule 1 (ICAM-1), which is involved in the adhesion and transmigration of circulating leukocytes [ 61 ]. Promising perspectives come from other blood proinflammatory biomarkers as midregional proenkephalin A (MR-PENK A), mainly associated with pain sensation, cardiac function, and immunity, which has been positively associated with increased risk of VaD [ 62 ].…”

An experimentally validated approach to automated biological evidence generation in drug discovery using knowledge graphs

“…The evidence chains also predict Ibudilast as a possible treatment for FXS through proenkephalin ( PENK ). PENK is an endogenous opioid polypeptide hormone that has been implicated in neuroinflammation and identified as an early indicator of vascular dementia 55 . Although neuroinflammation in FXS is still a contentious topic, microglia and astrocytes from FXS mice have been shown to produce an elevated proinflammatory cytokine response when activated 56 , 57 .…”

Paracrine Interleukin 6 Induces Cerebral Remodeling at Early Stages After Unilateral Common Carotid Artery Occlusion in Mice

“…The results were ambivalent regarding functional and cognitive effects. On the one hand, we observed protein regulations that would have unfavorable effects: upregulation of Sncg is associated with neurodegenerative diseases (29), and high circulating levels of Penk have been established as a marker for vascular dementia (30). We observed a reduction of Cstb, Jam3, Zc3h14, and Msn, which can cause neuroinflammation and epilepsy (Cstb) (31), bloodbrain-barrier disruption (Jam3) (20), impairment of synaptic function (Zc3h14) (32) and long-term memory (Msn) (18).…”