Prion-Protein-interacting Amyloid-β Oligomers of High Molecular Weight Are Tightly Correlated with Memory Impairment in Multiple Alzheimer Mouse Models*
| Autor: | Laura T. Haas, Mikhail A. Kostylev, Alexander O. Vortmeyer, Haakon B. Nygaard, Adam C. Kaufman, Pujan R. Patel, Stephen M. Strittmatter, Erik C. Gunther |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Genetically modified mouse
Male Prions Prefrontal Cortex Mice Transgenic Biology Biochemistry Presenilin law.invention Mice law Alzheimer Disease mental disorders PSEN1 medicine Presenilin-1 Memory impairment Animals Humans PrPC Proteins Prefrontal cortex Protein Structure Quaternary Molecular Biology Aged Aged 80 and over Memory Disorders Amyloid beta-Peptides Behavior Animal Molecular Bases of Disease Cell Biology Human brain respiratory system Middle Aged medicine.disease Mice Mutant Strains Recombinant Proteins Mice Inbred C57BL Molecular Weight Disease Models Animal medicine.anatomical_structure Recombinant DNA Female Alzheimer's disease Neuroscience human activities |
| Popis: | Alzheimer disease (AD) is characterized by amyloid-β accumulation, with soluble oligomers (Aβo) being the most synaptotoxic. However, the multivalent and unstable nature of Aβo limits molecular characterization and hinders research reproducibility. Here, we characterized multiple Aβo forms throughout the life span of various AD mice and in post-mortem human brain. Aβo exists in several populations, where prion protein (PrPC)-interacting Aβo is a high molecular weight Aβ assembly present in multiple mice and humans with AD. Levels of PrPC-interacting Aβo match closely with mouse memory and are equal or superior to other Aβ measures in predicting behavioral impairment. However, Aβo metrics vary considerably between mouse strains. Deleting PrPC expression in mice with relatively low PrPC-interacting Aβo (Tg2576) results in partial rescue of cognitive performance as opposed to complete recovery in animals with a high percentage of PrPC-interacting Aβo (APP/PSEN1). These findings highlight the relative contributions and interplay of Aβo forms in AD. Background: Amyloid-β (Aβ) oligomers are key in Alzheimer disease (AD) but are diverse and poorly characterized. Results: Multiple Aβ forms were measured across the life span of AD model mice and human AD brain. Conclusion: Aβ species interacting with prion protein were tightly linked to behavioral impairment. Significance: An Aβ oligomer subset with defined biochemical properties is present in multiple AD-relevant samples. |
| Databáze: | OpenAIRE |
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