Biology subjects

Anschuetz, A.

Publications and source records attributed to Anschuetz, A..

2 recordsLinked to original sources

bioRxiv2025

The Icelandic mutation APPA673T on amyloid-β plaque burden in the 5xFAD Alzheimer model

The protective Icelandic mutation in the amyloid precursor protein (APP) gene, APPA673T, identified in Icelandic and other Nordic populations is associated with a significantly lower risk of developing Alzheimers disease (AD). Conflicting results have been reported for the APPA673T mutation in various knock-in models of AD, but its effect in 5x familial AD (5xFAD) mice has never been investigated. We have crossed C57Bl6/J mice expressing a single point mutation edited into the murine APP gene via CRISPR-Cas gene editing, termed APPA673T, with 5xFAD mice that overexpress human APP carrying the Swedish (K670N/M671L), Florida (I716V), and London (V717I) mutations as well as human presenilin-1 (PS1) with two mutations (M146L and L286V); the resulting mice were termed 5xFADxAPPA673T. We have investigated amyloid beta (A{beta}) pathology in 5xFADxAPPA673T, 5xFAD and their respective controls, APPA673T and C57Bl6/J wild types, at 6-months of age using immunohistochemistry, immunoblotting, and ELISAs. We found a moderate yet significant reduction for A{beta} plaque size in male 5xFADxAPPA673T compared to 5xFAD. No differences were observed for soluble/insoluble A{beta}40 and A{beta}42 levels per se, but lower plaque count/area was found in 5xFADxAPPA673T when A{beta}42/A{beta}40 ratios were low, suggesting a genotype-dependent sensitivity to A{beta} aggregation and accumulation. Therefore, the APPA673T mutation has the potential to modify A{beta} pathology in 5xFAD mice at the age of 6 months.

neuroscience↗

bioRxiv2025

The effect of the Icelandic mutation APPA673T in the line 66 model of tauopathy

The Icelandic mutation in the amyloid precursor protein (APP), APPA673T, has been identified in Icelandic and Scandinavian populations and is associated with a significantly lower risk of developing Alzheimers disease (AD). Although this mutation led to reduction in amyloid {beta}-protein (A{beta}) production, its effect on tau pathology is not well studied. We have crossed line 66 (L66) tau transgenic mice that overexpress the P301S aggregation-prone form of tau with C57Bl6/J mice expressing a single point mutation edited into the murine APP gene via CRISPR-Cas gene editing, termed APPA673T. We have performed ELISA, histopathological and behavioural analyses of heterozygous male/female L66 and L66xAPPA673T crosses at the age of 6 months to investigate the effect of the A673T mutation on tau brain pathology and behavioural deficits in these mice. Using immunohistochemistry, we found only a moderate, yet significant, reduction of mAb 7/51-reactive tau in prefrontal cortex for L66xAPPA673T compared to L66 mice. Quantification of tau in soluble/insoluble brain homogenate fractions by ELISA confirmed the lack of overt differences between genotypes, as did our extensive behavioural phenotyping using six different paradigms accessing motor function, olfaction, depression/apathy-like behaviour, as well as exploration and sociability. Therefore, the APPA673T mutation does not appear to modulate tau pathology or motor and neuropsychiatric behaviour in L66 tau transgenic mice.

neuroscience↗