DEVELOPMENT OF PATHOLOGY IN YOUNG TG2576 MICE

MRI imaging in detecting the development of pathology in young Tg2576 mice

MRI imaging in detecting the development of pathology in young Tg2576 mice

Discussion

Summary of Results

More than 340 BNs in cases with infarction and more than 140 BNs in cases with neurodegenerative diseases were observed. The two polyclonal antibodies against ApoE (ApoEC and ApoEAB947) gave essentially identical results. BNs in infarction, in all the cases examined, exhibited an intense ApoE-like IR. In neurodegenerative diseases, this ApoE-like IR in BNs was absent or less intense. An ROI for the motor cortex (indicated by arrows) was placed on T1- (A), T2- (B), and T2*-(C) maps of Tg2576 and Wild-type (WT) mouse brain at approximately Bregma -2.18 mm.

Examination of the images obtained here did not reveal any obvious dark spots in T2*-weighted images of either male or female Tg2576 brains, indicating that no Aß plaques are present in these transgenic mice. Furthermore, there were no discernable differences between male and female Tg2576 or wild-type mice.

ROIs from the structural images were used on the T1, T2 and T2* maps to obtain the signal intensities, using Image J. Females and males were first analysed separately to determine if there was any effect of gender on the values obtained. The data were then combined to determine if there were any differences between Tg2576 and wild-type mice of both genders

No significant differences in the T1, T2 or T2*-weighted readings obtained from the HT, amygdala, MC and SC were obtained in either male or female Tg2576 mice when compared to their respective controls. However, there was a trend towards a significant decrease in T2* readings in the SC of Tg2576 mice when compared to their wild-type controls (Fig. 13, p=0.097).

Critical Analysis

Several tau mutations have been reported to be associated with frontal temporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), but none have been associated with AD (Gendron and Petrucelli 2009). A number of transgenic mice models that express human tau with FTDP-17 mutations have been produced. Some of these mice display NFTs, neuronal death and behavioral deficits. In addition, 1 Tg mice model that expresses a mutated (N279K) tau shows behavioral deficits without formation of NFTs or neuronal loss. In most of these models there is disruption of axon transport due to the tau expression that induces synaptic and neuronal loss. Another Tg tau mice model was developed expressing the mutated P301S tau which shows synaptic loss that precedes tangles formation.

In order to generate a more ideal model for AD, other researchers have used a single wild-type human tau to generate a transgenic model; however, most of these models did not develop NFTs, with the exception of two models: One expressing ON3R wild-type tau with a few NFTs in aged animals and another with abundant NFTs that expresses all six human tau isoforms on a knockout background for murine tau. The absence of tangles in mice that express a single wild-type human tau is likely due to the endogenous tau inhibiting the formation of ...