1 research outputs found
Elucidating Molecular Mass and Shape of a Neurotoxic Aβ Oligomer
Alzheimer's
disease (AD), the most prevalent type of dementia,
has been associated with the accumulation of amyloid β oligomers
(AβOs) in the central nervous system. AβOs vary widely
in size, ranging from dimers to larger than 100 kDa. Evidence indicates
that not all oligomers are toxic, and there is yet no consensus on
the size of the actual toxic oligomer. Here we used NU4, a conformation-dependent
anti-AβO monoclonal antibody, to investigate size and shape
of a toxic AβO assembly. By using size-exclusion chromatography
and immuno-based detection, we isolated an AβO-NU4 complex amenable
for biochemical and morphological studies. The apparent molecular
mass of the NU4-targeted oligomer was 80 kDa. Atomic force microscopy
imaging of the AβO-NU4 complex showed a size distribution centered
at 5.37 nm, an increment of 1.5 nm compared to the size of AβOs
(3.85 nm). This increment was compatible with the size of NU4 (1.3
nm), suggesting a 1:1 oligomer to NU4 ratio. NU4-reactive oligomers
extracted from AD human brain concentrated in a molecular mass range
similar to that found for in vitro prepared oligomers, supporting
the relevance of the species herein studied. These results represent
an important step toward understanding the connection between AβO
size and toxicity