4.0 Article

Soluble amyloid beta-containing aggregates are present throughout the brain at early stages of Alzheimer's disease

Journal

BRAIN COMMUNICATIONS
Volume 3, Issue 3, Pages -

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/braincomms/fcab147

Keywords

Alzheimer's disease; neurodegeneration; neuroinflammation; amyloid beta 42; soluble aggregates

Funding

  1. Biotechnology and Biological Sciences Research Council
  2. AstraZeneca
  3. Eisai-UK Dementia Research Institute research fellowship
  4. King's College research associateship
  5. UK Dementia Research Institute from DRI Ltd - UK Medical Research Council
  6. Alzheimer's Society
  7. Alzheimer's Research UK
  8. European Research Council [669237]
  9. Royal Society
  10. MRC [UKDRI-2003] Funding Source: UKRI

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Protein aggregation may be central to the pathogenesis of Alzheimer's disease, with soluble amyloid beta-containing aggregates found in various regions of the brain causing inflammation. Research suggests that aggregation occurs throughout the brain rather than spreading as the disease progresses, with different brain regions in different stages of the same process.
Protein aggregation likely plays a key role in the initiation and spreading of Alzheimer's disease pathology through the brain. Soluble aggregates of amyloid beta are believed to play a key role in this process. However, the aggregates present in humans are still poorly characterized due to a lack of suitable methods required for characterizing the low concentration of heterogeneous aggregates present. We have used a variety of biophysical methods to characterize the aggregates present in human Alzheimer's disease brains at Braak stage III. We find soluble amyloid beta-containing aggregates in all regions of the brain up to 200nm in length, capable of causing an inflammatory response. Rather than aggregates spreading through the brain as disease progresses, it appears that aggregation occurs all over the brain and that different brain regions are at earlier or later stages of the same process, with the later stages causing increased inflammation.

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