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• W4312087785 abstract "Background Matrix metalloproteinase-9 (MMP-9) is a proinflammatory, proteolytic enzyme that is dysregulated in Apolipoprotein (APOE) ε4 carriers, patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) and has been shown to accelerate tau oligomerization, blood-brain barrier breakdown and amyloid-β (Aβ) accumulation. Evidence suggests that MMP-9 activity may be regulated by sex hormones, yet it is unknown whether the association between plasma MMP-9 and cerebrospinal fluid (CSF) AD biomarker levels varies by sex. Method In 335 ADNI participants (128 women, mean age 74.8±7.4), including 56 cognitively normal adults, 183 MCI patients and 96 AD dementia patients, we examined whether sex modulates total and free plasma MMP-9 associations with CSF total tau (t-tau), tau phosphorylated at threonine 181 (p-tau181) and Aβ42. Result Free and total plasma MMP-9 levels were not associated with sex, age, APOE ε4 status or cardiovascular disease risk (CVDR). Total plasma MMP-9 levels were higher in AD dementia patients versus MCI patients but did not differ between normal controls and MCI or AD patients. Free and total MMP-9 levels were not associated with CSF Aβ42 regardless of sex. There was a sex × total plasma MMP-9 interaction on CSF t-tau (β=24.7; 95% CI, 82.5 to 355.2; P=0.002) and p-tau181 (β=24.7; 95% CI, 8.9 to 40.4; P=0.002). Higher total MMP-9 correlated with higher t-tau and p-tau181 levels in women, but with lower levels in men. There was a sex × free plasma MMP-9 interaction on CSF p-tau181 (β=19.5; 95% CI, 6.0 to 33.1; P=0.005) and t-tau (β=147.8; 95% CI, 30.2 to 265.3; P=0.01). Higher free plasma MMP-9 correlated with lower CSF p-tau181 and t-tau in men, but not women. These relationships were independent of age, education, diagnosis, CVDR, and CSF Aβ42 levels, and were likely driven by APOE ε4-carriers as free or total MMP-9 levels were not significantly associated with CSF biomarkers among non-carriers regardless of sex. Conclusion Our findings provide preliminary evidence of sex differences in associations between MMP-9 and CSF tau biomarkers, particularly among APOE ε4-carriers. Compared to male ε4-carriers, female ε4-carriers might be more vulnerable to MMP-9 activity, possibly promoting higher levels of AD-related tau pathology." @default.
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• W4312087785 date "2022-12-01" @default.
• W4312087785 modified "2023-10-16" @default.
• W4312087785 title "The relationship between plasma matrix metalloproteinase‐9 and cerebrospinal fluid biomarkers of tau is sex‐dependent" @default.
• W4312087785 doi "https://doi.org/10.1002/alz.064323" @default.
• W4312087785 hasPublicationYear "2022" @default.
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