Alzheimer’s Plaque Affects Different Brain Cells Differently

Summary: Alzheimer’s linked protein, amyloid beta, appears to do very little harm to glial cells, at least in fruit flies, researchers report.

Source: Linköping University.

Amyloid beta, a protein linked with Alzheimer’s disease, has different properties in different cell types in the brains of fruit flies. This is the conclusion of a study led by researchers at Linköping University in Sweden. While amyloid beta is highly toxic for nerve cells, it seems that certain other types of cell are hardly damaged at all by aggregates of the protein.

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Aggregated Aβ1-42 is selectively toxic for neurons, whereas glial cells produce mature fibrils with low toxicity in Drosophila

Highlights •Expressed Aβ1-42 aggregates profoundly in various cell types of Drosophila •Aβ1-42 accumulates as extracellular amyloid fibrils when expressed in glial cells •Aβ1-42 is highly toxic to neurons in Drosophila •Immature intracellular aggregates are more toxic than mature fibrillar Aβ1-42

Summary The basis for selective vulnerability of certain cell types for misfolded proteins (MPs) in neurodegenerative diseases is largely unknown. This knowledge is crucial for understanding disease progression in relation to MPs spreading in the CNS. We assessed this issue in Drosophila by cell-specific expression of human Aβ1-42 associated with Alzheimer’s disease. Expression of Aβ1-42 in various neurons resulted in concentration-dependent severe neurodegenerative phenotypes, and intraneuronal ring-tangle-like aggregates with immature fibril properties when analyzed by aggregate-specific ligands. Unexpectedly, expression of Aβ1-42 from a pan-glial driver produced a mild phenotype despite massive brain load of Aβ1-42 aggregates, even higher than in the strongest neuronal driver. Glial cells formed more mature fibrous aggregates, morphologically distinct from aggregates found in neurons, and was mainly extracellular. Our findings implicate that Aβ1-42 cytotoxicity is both cell and aggregate morphotype dependent.

Source: Leah Russell – Linköping University Publisher: Organized by Image Source: image is credited to Jonson et al./Cell Chemical Biology. Original Research: Abstract for “Aggregated Aβ1-42 is selectively toxic for neurons, whereas glial cells produce mature fibrils with low toxicity in Drosophila” by Maria Jonson, Sofie Nyström, Alexander Sandberg, Marcus Carlback, Wojciech Michno, Jörg Hanrieder, Annika Starkenberg, K. Peter R. Nilsson, Stefan Thor and Per Hammarström in Cell Chemical Biology. Published April 12 2018. doi:10.1016/j.chembiol.2018.03.006