. Abundance of Aβ₅-x like immunoreactivity in transgenic 5XFAD, APP/PS1KI and 3xTG mice, sporadic and familial Alzheimer's disease. Mol Neurodegener. 2014 Apr 2;9:13. PubMed.

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  1. The article by Guzman et al. provided immunohistochemical evidence that Aβ5-x, one of the N-truncated Aβ species, is more abundantly present in the brains of familial Alzheimer’s disease (FAD) cases than sporadic AD (SAD) cases. Vascular Aβ5-x immunoreactivity appeared stronger than the parenchymal staining in SAD cases, consistent with our previous report (Takeda et al., 2004). In contrast, Aβ5-x immunoreactivity was abundant in both extracellular plaques and vascular deposits in different FAD cases. Using cellular models, we demonstrated that Aβ5-40/42 is preferentially produced from the caspase-cleaved form of amyloid precursor protein (APP). Thus, abundant Aβ5-x immunoreactivity in FAD cases might be due to more pronounced caspase activation in FAD brains. Their data additionally showed AD model mice displayed Aβ5-x immunopositive deposits only in extracellular plaques with no intraneuronal Aβ5-x immunoreactiviy, suggesting that Aβ5-x may not contribute to early neuronal degeneration. This finding is also in agreement with our prior data that the majority of intracellular Aβ consists of Aβ1-40/42 in cells expressing the caspase-cleaved form of APP (Takeda et al., 2004). It is likely that Aβ5-x is generated mainly in the extracellular Aβ pathway. 

    References:

    . Amino-truncated amyloid beta-peptide (Abeta5-40/42) produced from caspase-cleaved amyloid precursor protein is deposited in Alzheimer's disease brain. FASEB J. 2004 Nov;18(14):1755-7. PubMed.

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Research Models

  1. 5xFAD (C57BL6)