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Intracerebroventricular Injection of Amyloid-β Peptides in Normal Mice to Acutely Induce Alzheimer-like Cognitive Deficits
Published on: March 16, 2016
Aβ∗56 is a stable oligomer that impairs memory function in mice
Peng Liu1,2, Ian P Lapcinski1,2, Chris J W Hlynialuk1,2
1N. Bud Grossman Center for Memory Research and Care, Minneapolis, MN 55455, USA.
Abstract:
Amyloid-β (Aβ) oligomers consist of fibrillar and non-fibrillar soluble assemblies of the Aβ peptide. Aβ∗56 is a non-fibrillar Aβ assembly that is linked to memory deficits. Previous studies did not decipher specific forms of Aβ present in Aβ∗56. Here, we confirmed the memory-impairing characteristics of Aβ∗56 and extended its biochemical characterization. We used anti-Aβ(1-x), anti-Aβ(x-40), anti-Aβ(x-42), and A11 anti-oligomer antibodies in conjunction with western blotting, immunoaffinity purification, and size-exclusion chromatography to probe aqueous brain extracts from Tg2576, 5xFAD, and APP/TTA mice. In Tg2576, Aβ∗56 is a ∼56-kDa, SDS-stable, A11-reactive, non-plaque-dependent, water-soluble, brain-derived oligomer containing canonical Aβ(1-40). In 5xFAD, Aβ∗56 is composed of Aβ(1-42), whereas in APP/TTA, it contains both Aβ(1-40) and Aβ(1-42). When injected into the hippocampus of wild-type mice, Aβ∗56 derived from Tg2576 mice impairs memory. The unusual stability of this oligomer renders it an attractive candidate for studying relationships between molecular structure and effects on brain function.
Insights
Amyloid-beta*56 (Aβ*56) oligomers impair memory. This study biochemically characterized Aβ*56, revealing its distinct peptide compositions across different mouse models, offering insights into Alzheimer
Area of Science:
- Neuroscience
- Biochemistry
- Molecular Biology
Background:
- Amyloid-beta (Aβ) oligomers are implicated in cognitive decline.
- Aβ*56 is a specific soluble Aβ assembly linked to memory deficits.
- The precise molecular composition of Aβ*56 has remained unclear.
Purpose of the Study:
- To confirm the memory-impairing effects of Aβ*56.
- To biochemically characterize the Aβ peptide forms within Aβ*56 across different transgenic mouse models.
- To investigate the structural stability and properties of Aβ*56.
Main Methods:
- Utilized antibodies targeting different Aβ forms and oligomers (A11).
- Employed western blotting, immunoaffinity purification, and size-exclusion chromatography.
- Analyzed brain extracts from Tg2576, 5xFAD, and APP/TTA mouse models.
- Injected Aβ*56 into the hippocampus of wild-type mice.
Main Results:
- Confirmed Aβ*56's memory-impairing properties.
- Determined Aβ*56 composition varies: Aβ(1-40) in Tg2576, Aβ(1-42) in 5xFAD, and both in APP/TTA mice.
- Characterized Aβ*56 as an SDS-stable, water-soluble, non-plaque-dependent oligomer.
Conclusions:
- Aβ*56's molecular composition is model-dependent.
- The stability and specific Aβ forms within Aβ*56 are key to its cognitive effects.
- Aβ*56 is a valuable target for understanding the link between molecular structure and brain function in Alzheimer's disease.
