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Comment & Response
DZ𳾲11, 2024

Gantenerumab in Dominantly Inherited Alzheimer Disease—Reply

Author Affiliations
  • 1Department of Neurology, Ludwig-Maximilians-Universität München, Munich, Germany
  • 2German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
  • 3Department of Neurology, Washington University School of Medicine in St Louis Continuing Medical Education, St Louis, Missouri
JAMA Neurol. Published online November 11, 2024. doi:10.1001/jamaneurol.2024.3828

In Reply Pomara and Imbimbo raise important points in their letter regarding our recent publication.1 Specifically, they offer additional considerations for the increases of the soluble form of triggering receptor expressed on myeloid cells 2 (sTREM2) in participants receiving gantenerumab compared with placebo. We appreciate the chance to address the points raised.

In the context of sporadic and genetic forms of Alzheimer disease (AD), sTREM2 has been shown to increase in early stages of cognitive impairment while plateauing in the later symptomatic stages.2,3 On the subject of protective effects of sTREM2 against AD pathophysiology, observations have been somewhat ambiguous, with studies finding that individuals with higher baseline sTREM2 progress more slowly and that levels of sTREM2 correlate inversely with amyloid and tau burden as assessed by positron emission tomography, while it has also been reported that certain variations in the TREM2 gene, resulting in elevated sTREM2 levels due to increased shedding, seem to be associated with higher risk of AD.4

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