Details

Autor(en) / Beteiligte

• Ferrari‐Souza, João Pedro
• Ferreira, Pamela C.L.
• Bellaver, Bruna
• Povala, Guilherme
• Lussier, Firoza Z
• Leffa, Douglas Teixeira
• Therriault, Joseph
• Tissot, Cécile
• Soares, Carolina
• Benedet, Andrea Lessa
• Wang, Yi‐Ting
• Chamoun, Mira
• Servaes, Stijn
• Macedo, Arthur C.
• Vermeiren, Marie
• Bezgin, Gleb
• Kang, Min Su
• Stevenson, Jenna
• Rahmouni, Nesrine
• Pallen, Vanessa
• Poltronetti, Nina Margherita
• Aguzzoli, Cristiano Schaffer
• Zalzale, Hussein
• Rohden, Francieli
• Cohen, Annie
• Lopez, Oscar L.
• Tudorascu, Dana
• Klunk, William E
• Villemagne, Victor L
• Souza, Diogo O.
• Schilling, Lucas Porcello
• Karikari, Thomas K
• Soucy, Jean‐Paul
• Gauthier, Serge
• Zimmer, Eduardo R
• Rosa‐Neto, Pedro
• Pascoal, Tharick A.

Titel

Potential utility of using both APOEε4 and Aβ positivity to enrich clinical trials of tau‐targeting therapies

Ist Teil von

• Alzheimer's & dementia, 2023-12, Vol.19 (S16), p.n/a

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Background The use of enrichment strategies is crucial for selecting individuals with the highest probability of Alzheimer’s disease (AD)‐related progression in typical clinical trial time frames. Although both amyloid‐β (Aβ) pathology and the apolipoprotein E ε4 (APOEε4) genotype have been shown to accelerate tau accumulation, it is still not clear whether assessing both APOEε4 genotype and Aβ positivity is useful to enrich tau‐targeting trials using tau positron emission tomography (PET) as outcome. Here, we investigated the implications of considering APOEε4 carriership for population enrichment in trials testing drug effects on tau tangle deposition in cognitively impaired (CI) individuals across the AD continuum. Method We studied 29 Aβ positive CI individuals (16 with mild cognitive impairment [MCI] and 13 with AD dementia) from the McGill Translational Biomarkers in Aging and Dementia (TRIAD) cohort. Study participants underwent clinical assessments, APOE genotyping, magnetic resonance imaging, PET for Aβ ([18F]AZD4694) and tau ([18F]MK6240) at baseline, as well as a follow‐up tau‐PET scan (mean follow‐up, 2.2 years). Aβ positivity was determined as global [18F]AZD4694 SUVR ≥ 1.55. Result No demographic differences were observed between APOEε4 carriers and noncarriers (Table 1). Regression analysis revealed that APOEε4 carriers had higher tau‐PET SUVR increase in temporal regions compared to APOEε4 noncarriers (Figure 1). The use of Aβ positivity alone for population enrichment of a clinical trial focusing on CI individuals would require a sample size of 436 individuals per study arm to test a 25% drug effect on tau‐PET accumulation (Figure 2). A similar clinical trial with a population enrichment strategy using Aβ positivity plus APOEε4 carriership would require a sample size of as few as 158 individuals per study arm (reduction of 64% in relation to using only Aβ positivity) to test the same drug effect (Figure 2). Conclusion Our results reveal that APOEε4 carriership is associated with increased tau tangle accumulation in CI individuals who are Aβ positive. Clinical trials testing drug effects on tangle deposition may benefit from assessing both APOEε4 carriership and Aβ positivity statuses as enrollment criteria to select individuals at higher risk of fast tau accumulation, resulting in a more cost‐effective trial.