School of Biomedical Sciences cordially invites you to join the following Post-doctoral Fellow (PDF) Seminar:

Date: 6 May 2025 (Tuesday)
Time: 4:00 pm – 4:30 pm
Venue: Seminar Room 2, G/F, Laboratory Block, 21 Sassoon Road
Host: Dr. Haifeng Fu

Light refreshments will be served. Please register via the below link by 5 May 2025 (Monday):
Registration: https://hku.au1.qualtrics.com/jfe/form/SV_e4pjsJP7wY66jgG

Cryo-EM reveals distinct fibril architecture of Aβ filaments from Alzheimer’s disease brain with the Flemish mutation
Dr. Peerzada Shariq Shaheen Khaki (Post-doctoral Fellow)
[Supervisor: Professor Rubén Hervas Millan]

Alzheimer’s disease (AD) is characterized by the aggregation of amyloid beta (Aβ) into pathological filaments, which, along with other factors, contribute to neurodegeneration and cerebral amyloid angiopathy (CAA). The Flemish mutation (A692G) in the APP gene is linked to early onset dementia and severe CAA. Nevertheless, the structural mechanisms underlying the disease's progression remain unclear. Here, we report the high resolution cryo-electron microscopy (cryo-EM) structure of Aβ filaments isolated from post-mortem human AD brain carrying the Flemish mutation. Structural analysis revealed the Aβ filaments as Aβ40, forming a unique fibril architecture composed of two proto-filaments, z-shaped, arranged with C2 symmetry. As a result of the Flemish mutation, the substitution of alanine to glycine confers a distinct fibril fold, differing from wild type Aβ40 and Aβ42 filaments previously resolved in AD brains. Mutation specific conformational rearrangements reshape proto-filament interactions, directly linking the Flemish variant to fibril polymorphism. The structural insights gathered advance our understanding of mutation driven fibril polymorphism in AD and highlight the potential for structure guided therapeutic approaches targeting pathogenic Aβ conformers.

All are welcome.