Non‐fibrillar β‐amyloid exerts toxic effect on neuronal cells

Alzheimer's disease is the most common form of dementia and no cure is known so far. Extensive genetic works and in vitro experiments combined with clinical observations link amyloid β‐protein (Aβ) to the pathogenesis of Alzheimer's disease (AD). It was hypothesized that Aβ becomes toxic when it adopts a fibrillar conformation. Recently, non‐fibrillar form of Aβ was observed and the potential role in the pathogenesis of AD became an interesting subject. In this study, the cytotoxicity of non‐fibrillar Aβ and fibrillar Aβ was compared on oxidative stress, membrane damage, or nucleosome break down. Non‐fibrillar Aβ was not toxic in peripheral nervous system‐derived cells but significantly toxic in central nervous system‐derived cells while fibrillar Aβ was non‐selectively toxic in both cell culture. The neurotoxicity of non‐fibrillar Aβ was reproduced in semi‐in vivo culture of mouse brain slice. In conclusion, non‐fibrillar Aβ could be more relevant to the selective neurodegeneration in Alzheimer's brains than fibrillar Aβ and further research needs to be done for identification of the cause of AD.

Key words:

• Alzheimer's disease
• β‐Amyloid
• NT2
• SHSY5Y
• Slice
• Neurotoxicity

Notes

To whom correspondence should be addressed. Tel: [phone], Fax: [phone], E‐mail: [email protected]