Circadian and sleep phenotypes in a mouse model of Alzheimer's disease characterized by intracellular accumulation of amyloid β oligomers.

Disturbances in sleep-wake and circadian rhythms may reportedly precede the onset of cognitive symptoms in the early stages of Alzheimer's disease (AD); however, the underlying mechanisms of these AD-induced sleep disturbances remain unelucidated. To specifically evaluate the involvement of amyloid beta (Aβ) oligomers in AD-induced sleep disturbances, we examined circadian and sleep phenotypes using an Aβ-GFP transgenic (Aβ-GFP Tg) mouse characterized by intracellular accumulation of Aβ oligomers. The circadian rhythm and free-running period of wheel running activity were identical between Aβ-GFP Tg and littermate wild-type mice.

Mulberry fruit extract alleviates the intracellular amyloid-β oligomer-induced cognitive disturbance and oxidative stress in Alzheimer's disease model mice.

Intracellular amyloid-β (Aβ) oligomers are key therapeutic targets because they are strongly cytotoxic and play crucial roles in the cognitive function in Alzheimer's disease (AD). Anthocyanins, polyphenolic flavonoids with antioxidant and neuroprotective properties, are potential therapeutic candidates for AD. Here, we investigated the effects of anthocyanin-enriched extracts from fruits of mulberry (Morus alba Linn.

New Alzheimer's disease model mouse specialized for analyzing the function and toxicity of intraneuronal Amyloid β oligomers.

Oligomers of intracellular amyloid β protein (Aβ) are strongly cytotoxic and play crucial roles in synaptic transmission and cognitive function in Alzheimer's disease (AD). However, there is currently no AD model mouse in which to specifically analyze the function of Aβ oligomers only. We have now developed a novel AD model mouse, an Aβ-GFP transgenic mouse (Aβ-GFP Tg), that expresses the GFP-fused human Aβ protein, which forms only Aβ oligomers within neurons throughout their life.

Development of new fusion proteins for visualizing amyloid-β oligomers in vivo.

The intracellular accumulation of amyloid-β (Aβ) oligomers critically contributes to disease progression in Alzheimer's disease (AD) and can be the potential target of AD therapy. Direct observation of molecular dynamics of Aβ oligomers in vivo is key for drug discovery research, however, it has been challenging because Aβ aggregation inhibits the fluorescence from fusion proteins. Here, we developed Aβ1-42-GFP fusion proteins that are oligomerized and visualize their dynamics inside cells even when aggregated.

Immunohistochemical detection of the delayed formation of nonfibrillar large amyloid-β aggregates.

The occurrence of senile plaques consisting of amyloid-β protein (Aβ) is a major neuropathological hallmark of Alzheimer's disease (AD). We previously developed and characterized monoclonal antibodies 31-2 and 75-2 that specifically bind to nonfibrillar Aβ1-42 aggregates with diameters of more than 220 and 50 nm, respectively. Here, we report the use of these antibodies to examine the aggregation of exogenous Aβ1-42 in cultured rat hippocampal neurons.