Target Engagement and Cognitive Outcomes of Anti-Amyloid Immunotherapies in Early-Onset Alzheimer’s Disease - First Report from the LEADS Study

Q: What was the study’s main goal?

To assess target engagement and cognitive outcomes of anti-amyloid immunotherapies in early-onset Alzheimer’s disease using observational LEADS data.

Q: What participants and treatments were included?

The analysis used 20 early-onset Alzheimer’s disease participants treated with Aducanumab (n=4), Lecanemab (n=15), or a transition from Aducanumab to Lecanemab (one).

Q: What outcomes changed after treatment?

Aβ burden decreased significantly after treatment, while tau burden and CDR-SB trajectories showed no significant inflection. In treated-untreated comparisons, CDR-SB changes suggested a slower increase and Aβ levels decreased significantly, with no significant tau differences.

Sep 30, 2026

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Monoclonal antibodies targeting Aβ pathology demonstrate strong target engagement in trials, producing rapid Aβ clearance and slowing clinical decline. As these treatments are now used in practice, observational cohorts can evaluate real-world effects. This poster analyzes LEADS data from 20 early-onset Alzheimer’s disease participants treated with Aducanumab, Lecanemab, or both, using longitudinal Aβ and tau PET plus cognitive outcomes. Piecewise regression with a treatment-start knot estimates changes after initiation.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages4

Reading Time10 min

AccessFree to download

Abstract

Background

Method

Result

Conclusion

DOI: 10. 1002/alz70856_104661 BIOMARKERS POSTER PRESENTATION NEUROIMAGING Target Engagement and Cognitive Outcomes of Anti-Amyloid Immunotherapies in Early-Onset Alzheimer’s Disease: First Report from the LEADS Study Konstantinos Chiotis1 Ganna Blazhenets 1 Ani Eloyan2 Piyush Maiti 1 Jiaxiuxiu Zhang 1 Alexandra Touroutoglou3 Kala Kirby4 Dustin B. Hammers4 Maria C. Carrillo5 Brad C. Dickerson3 Liana G. Apostolova6, 7, 8 Gil D. Rabinovici 1, 9 the Longitudinal Early-Onset Alzheimer’s Disease Study Consortium 1 Memory and Aging Center, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA 2 Department of Biostatistics, Brown University, Providence, RI, USA 3 Frontotemporal Disorders Unit and Massachusetts Alzheimer’s Disease Research Center, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA 4 Indiana University School of Medicine, Indianapolis, IN, USA 5Alzheimer’s Association, Chicago, IL, USA 6 Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA 7 Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA 8 Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA 9 Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA Correspondence Konstantinos Chiotis, Memory and Aging Center, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA. [Email:](Email: Konstantinos.chiotis@ucsf.edu)[ Konstantinos.chiotis@ucsf.edu](Email: Konstantinos.chiotis@ucsf.edu) Abstract Background: In clinical trials, monoclonal antibodies targeting Aβ pathology have shown strong target engagement, resulting in rapid Aβ clearance and a deceleration in rate of clinical decline. Now that these treatments are approved and implemented in clinical practice, we could assess their effects in observational studies involving these patients. Method: We analyzed data from 20 participants with early-onset Alzheimer’s disease (EOAD) in the Longitudinal Early-Onset Alzheimer’s Disease Study (LEADS) cohort, treated with Aducanumab (n = 4), Lecanemab (n = 15), or both (one transitioning from Aducanumab to Lecanemab). All participants had MCI or mild dementia at baseline, longitudinal Aβ and tau PET, as well as cognitive assessments, with at least one observation before and after treatment initiation. We applied piecewise regression with a knot at the treatment start, to evaluate changes in Aβ and tau PET burden and Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores. We compared the trajectories of treated participants with an untreated group (i.e., treated-untreated comparison) from LEADS, matched for age, sex, APOE ε4 genotype, pretreatment Aβ and tau PET load, CDR-SB, and follow-up duration, using a 1:3 matching design. Result: The median treatment duration was 8 months (IQR=5-10). In the piecewise regression model, the treated group showed significant decreases in Aβ burden posttreatment (Δ=-52 Centiloids/yr, p <0.001) with widespread neocortical involvement (Figure 1). However, no significant inflection in tau burden (Δ=0SUVR/yr, p = 0. 58) or CDR-SB (Δ=0. 3 units/yr, p = 0. 57) trajectories was observed. In the treated-untreated comparison, the treated group showed a trend toward slower increases in CDR-SB This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2025 The Alzheimer’s Association. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association. Alzheimer’s Dement. 2025;21(Suppl. 2):e104661. [https://doi.org/10.1002/alz70856_104661](https://doi.org/10.1002/alz70856_104661

FAQs

What was the study’s main goal?

To assess target engagement and cognitive outcomes of anti-amyloid immunotherapies in early-onset Alzheimer’s disease using observational LEADS data.

What participants and treatments were included?

The analysis used 20 early-onset Alzheimer’s disease participants treated with Aducanumab (n=4), Lecanemab (n=15), or a transition from Aducanumab to Lecanemab (one).

What outcomes changed after treatment?

Aβ burden decreased significantly after treatment, while tau burden and CDR-SB trajectories showed no significant inflection. In treated-untreated comparisons, CDR-SB changes suggested a slower increase and Aβ levels decreased significantly, with no significant tau differences.

Sep 30, 2026

Uploaded by Mia