Altered brain arginine metabolism with age in the APPswe/PSEN1dE9 mouse model of Alzheimer's disease.

Amyloid-beta (Aß) cleaved from amyloid precursor protein (APP) has been proposed to play a central and causative role in the aetiology of Alzheimer's disease (AD). APPswe/PSEN1dE9 (APP/PS1) transgenic mice display chronic Aß accumulation and deposition in the brain. L-arginine is a semi-essential amino acid with a number of bioactive metabolites, and altered arginine metabolism has been implicated in the pathogenesis and/or the development of AD. This study systematically investigated how arginine metabolic profiles changed in the frontal cortex, hippocampus, parahippocampal region and cerebellum of male APP/PS1 mice at 4, 9 and 17 months of age relative to their sex- and age-matched wildtype controls. Immunohistochemistry demonstrated age-related Aß deposition in the brain. High-performance liquid chromatography and mass spectrometry revealed age-related increases in glutamine, spermidine and spermine in APP/PS1 mice in a region-specific manner. Notably, genotype-related increases in spermine were found in the frontal cortex at the 9-month age point and in the frontal cortex, hippocampus and parahippocampal region at 17 months of age. Given the existing literature indicating the role of polyamines (spermine in particular) in modulating the aggregation and toxicity of Aß oligomers, increased spermidine and spermine levels in APP/PS1 mice may be a neuroprotective mechanism to combat Aß toxicity. Future research is required to better understand the functional significance of these changes.

The reproducibility of facial approximation accuracy results generated from photo-spread tests.

The accuracies of facial approximations have been measured by determining the frequency that examiners recognize correctly matching faces from photo-spreads under blind conditions. However, the reliability of these studies is unknown and warrants investigation since photo-spread results are based on subjective judgements of typically small single groups of examiners (<150 individuals). Moreover, statistical significance tests hold limited value for gauging reliability since these probabilities are only applicable to exactly matched study samples. To redress this issue, this study measured the repeatability of photo-spread results using three previously published facial approximations, the same photo-spread from the original study, and four independent groups of examiners (the original study group (trial 1); and three retest groups: trial 2=c. 40 individuals; trial 3=c. 75 individuals; and trial 4=c. 115 individuals). Across all three facial approximations, differences in recognition rates varied from 0% to 31% between independent samples of examiners. For the nine faces that commonly received high recognition scores, the largest mean difference was 18%. This indicates that when a photo-spread size of 10 faces is used, the results generated from a sample of <115 examiners should be considered approximate, and that any differences in the recognition rates that do not exceed 18% should be considered to be negligible.

Measuring the accuracy of facial approximations: a comparative study of resemblance rating and face array methods.

The success of facial approximation is thought to depend, at least in part, upon the "accuracy" of the constructed face. However, methods of accuracy assessment are varied and this range in methods may be responsible for the disparate results reported in the literature. The aim of this study was to determine if the accuracy results of one facial approximation were comparable across two different assessment methods (resemblance ratings and simultaneous face array tests using unfamiliar assessors) and if resemblance ratings co-varied with recognition responses. True-positive recognition performance from the facial approximation was poor (21%) while resemblance scores using the same facial approximation were moderately high (3 out of 5 on a five-point scale). These results are not, therefore, consistent and indicate that either different variables are being evaluated by the methods, or the same variable is being examined but with different weight/calibration. Further resemblance ratings tests of the facial approximation to three foil faces from the face array revealed that resemblance scores were similar irrespective of which face was compared, and did not closely correspond with the degree of recognition performance. This was especially the case for isolated comparisons of single faces to the facial approximation. Collectively, these results indicate that resemblance ratings are: (i) insensitive measures of a facial approximation's accuracy; and (ii) inconsistent with results of unfamiliar simultaneous face-array recognition results. These data suggest that familiar and unfamiliar recognition tests should be given increased weight in contrast to current resemblance rating tests.