| Autor: |
Beckers, Elise, Riphagen, Joost M., Ashton, Nicholas J., Janelidze, Shorena, Blennow, Kaj, Hansson, Oskar, Zetterberg, Henrik, Jacobs, Heidi I.L., Van Egroo, Maxime |
| Zdroj: |
Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Dec2023 Supplement 24, Vol. 19, p1-2, 2p |
| Abstrakt: |
Background: The brainstem locus coeruleus (LC) constitutes the primary source of norepinephrine (NE) in the central nervous system and has been reported as one of the earliest accumulation sites of hyperphosphorylated tau protein in Alzheimer's disease (AD). Autopsy and animal studies suggested that this aggregation of hyperphosphorylated tau in the LC is associated with hyperactivity in LC neurons and elevated concentrations of NE metabolites. Here, we investigated whether elevated concentrations of 3‐methoxy‐4‐hydrophenylglycol (MHPG), a NE metabolite measured in the plasma, is associated with plasma phosphorylated tau, a biomarker of AD pathology. Method: Ninety‐eight cognitively unimpaired participants (age = 59.82 ± 13.13 [30‐84] y, 52 females, Table 1) underwent a blood draw. Plasma MHPG concentrations were measured and adjusted for NE. Levels of total tau, phosphorylated tau at threonine 181 (pTau181) and threonine 231 (pTau231) were quantified by single molecule array (Simoa), while phosphorylated tau at threonine 217 (pTau217) was quantified by the Meso Scale Discovery (MSD) platform. Multiple linear regression models tested for the relationship between MHPG concentrations and plasma levels of tau‐related measures, while controlling for age and sex. Result: PTau231 and MHPG concentrations were positively correlated (t = 2.26, p =.03, Figure 1). No significant relationships were found between MHPG and other phosphorylated tau biomarkers (all p >.23), but we observed a trend for a positive association with plasma total tau levels (t = 1.88, p =.06). Conclusion: Consistent with previous CSF studies as well as animal studies, we found that elevated NE metabolism co‐occurs with the earliest events in the phosphorylation cascade of tau proteins, suggesting an important role of a dysregulated NE system early in the AD pathophysiologic cascade. Future work will need to determine the evolution of theses associations as the disease progresses, potential effect modifications by beta‐amyloid and the downstream effects of these processes on cognition and behavior. [ABSTRACT FROM AUTHOR] |
| Databáze: |
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