Deciphering the Morphological Difference of Amyloid-β Fibrils in Familial and Sporadic Alzheimer's Diseases.

ABSTRACT: The aggregation of amyloid-β (Aβ) into amyloid fibrils is the major pathological hallmark of Alzheimer's disease (AD). Aβ fibrils can adopt a variety of morphologies, the relative populations of which are recently found to be associated with different AD subtypes such as familial and sporadic AD (fAD and sAD, respectively). The two AD subtypes differ in their ages of onset, AD-related genetic predispositions, and dominant Aβ fibril morphologies. We postulate that these disease subtype-dependent fibril morphology differences can be attributed to the intrinsic fibril properties and interacting molecules in the environment. Using atomistic discrete molecular dynamics simulations, we demonstrated that the fAD-dominant morphology exhibited a lower free-energy barrier for fibril growth but also

SUBMITTER: Huang G 

PROVIDER: S-EPMC11590496 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature