Brum WS, Docherty KF, Ashton NJ, Zetterberg H, Hansson O, McMurray JJ, Blennow K. Effect of Neprilysin Inhibition on Alzheimer Disease Plasma Biomarkers: A Secondary Analysis of a Randomized Clinical Trial. JAMA Neurol. 2024 Feb 1;81(2):197-200. PubMed.
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RIKEN Center for Brain Science
Nobuhisa Iwata, a former member of my laboratory and currently professor of Nagasaki University, quantified plasma Aβ40 and 42 in wild-type and neprilysin knockout mice. Aβ40 and 42 were 1.6 and 1.7 times higher in the knockout mice, respectively, and the difference was statistically significant. The difference in the Aβ42/40 ratio did not reach statistical significance, presumably due to the deviation of data although the sample size was relatively large (n = 6). Shirotani and colleagues are writing a brief report on this finding.
In any case, these data indicate that neprilysin inhibition in the cardiovascular system likely affects plasma Aβ levels, and that use of Aβ quantification for diagnosis of preclinical and clinical AD needs to be carefully interpreted.
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