Co-aggregation with Apolipoprotein E modulates the function of Amyloid-β in Alzheimer's disease
2021
Isoforms of Apolipoprotein E (ApoE) determine our risk of developing late-onset Alzheimers Disease (AD), but the mechanism underlying this link is poorly understood. In particular, the relevance of direct interactions between ApoE and Amyloid-{beta} (A{beta}) remains controversial. Here, single-molecule imaging shows that in the early stages of aggregation, all isoforms of ApoE associate with A{beta} in large co-aggregates, but then fall away as fibrillation happens. Similar large co-aggregates exist in the brains of AD patients, accounting for around 50% of the mass of aggregated A{beta} detected in the frontal cortices of homozygotes with the higher-risk APOE4 gene. The cellular uptake and toxicity of these large co-aggregates are isoform-dependent, suggesting a mechanistic role for ApoE-A{beta} interactions in AD.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
35
References
0
Citations
NaN
KQI