Details

Autor(en) / Beteiligte

• Ferrari‐Souza, João Pedro
• Bellaver, Bruna
• Ferreira, Pamela C.L.
• Benedet, Andrea Lessa
• Povala, Guilherme
• Lussier, Firoza Z
• Leffa, Douglas Teixeira
• Therriault, Joseph
• Tissot, Cécile
• Soares, Carolina
• 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
• Cohen, Annie
• Lopez, Oscar L.
• Klunk, William E
• Soucy, Jean‐Paul
• Gauthier, Serge
• Souza, Diogo O.
• Triana‐Baltzer, Gallen
• Saad, Ziad S.
• Kolb, Hartmuth C.
• Karikari, Thomas K
• Villemagne, Victor L
• Tudorascu, Dana
• Ashton, Nicholas J.
• Zetterberg, Henrik
• Blennow, Kaj
• Zimmer, Eduardo R
• Rosa‐Neto, Pedro
• Pascoal, Tharick A.

Titel

APOEε4 potentiates the effects of Aβ pathology on the deposition of neurofibrillary tangles via tau phosphorylation

Ist Teil von

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

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Wiley Online Library Journals

Beschreibungen/Notizen

• Background The mechanisms by which the apolipoprotein E ε4 (APOEε4) allele influences Alzheimer’s disease (AD) pathophysiological progression are poorly understood. Here, we tested the association of APOEε4 carriership and amyloid‐β (Aβ) burden with longitudinal tau pathology progression. Method We studied 104 individuals across the aging and AD clinical spectrum from the McGill TRIAD cohort. Study participants underwent clinical assessments, APOE genotyping, magnetic resonance imaging, positron emission tomography (PET) for Aβ ([18F]AZD4694) and tau ([18F]MK6240) at baseline, as well as an additional follow‐up tau‐PET scan (mean follow‐up, 2.4 years). We further assessed longitudinal changes in tau phosphorylation (plasma phosphorylated tau at threonine 217 [p‐tau217+]), brain atrophy (gray matter density), and clinical function (clinical dementia rating scale sum of boxes). Result We found that APOEε4 carriership potentiates Aβ effects on longitudinal tau tangle accumulation over two years (Figure 1). Interestingly, the APOEε4‐potentiated Aβ effects on tangles were mediated by longitudinal plasma p‐tau217+ increase (Figure 2). In addition, this longitudinal tau accumulation as measured by PET was accompanied by brain atrophy and clinical decline during the follow‐up period (Figure 3). Conclusion Our results support a model in which the APOEε4 allele plays a key role in Aβ downstream effects on the aggregation of phosphorylated tau in the form of neurofibrillary tangles in the living human brain, which is a key factor in the development of dementia. These observations have important implications for the design of future trials by suggesting that the combination of therapies targeting both ApoeE4 and Aβ pathology might have the potential to synergistically halt tau progression in AD.