We will continue presenting Case Study publications that have received a lot of interest among the scientific community (and sometimes even in mass media) and are particularly interesting from the GSP perspective. We hope that these cases will be useful in training programs and will help younger scientists to learn about the basics of study design, planning and analysis.
This month we chose: vom Berg et al. (2012) Inhibition of IL­12/IL­23 signaling reduces Alzheimer’s disease–like pathology and cognitive decline. Nature Med 18 (12): 1812-9.

There are many aspects of this report that are worth discussing. However, the most interesting part is the behavioural data. According to the conclusion stated in the article, intracerebroventricular delivery of a neutralizing p40-specific antibody (p40 is the common IL-12 and IL-23 subunit) reversed cognitive deficits in aged APPPS1 mice (“Alzheimer” mouse). This conclusion is based on the experiments using three cognitive tasks (discussed on pp. 1816-7): the contextual fear conditioning paradigm, novel object recognition and the Barnes maze. So, how strong is the evidence?
Contextual fear conditioning: Data is not shown – apparently because ‘…performance in the contextual fear conditioning test did not differ between p40-antibody-treated and isotype-treated APPPS1 mice’. In other words, no effects of treatment.
Novel object recognition: Data is presented in Fig. 5a but it is difficult to see any support for either ‘deficits shown by APPPS1 mice treated with isotype control antibodies’ (vs. corresponding WT mice) or normalization ‘p40-antibody treatment to the levels of age-matched WT mice’. While the study design is 2×2, results of one-way ANOVA are presented with no signs that pairwise group comparisons were conducted to support the conclusions made (Dunnett’s test is mentioned in the legend referring to Fig. 5a and, in any case, deals with comparing all groups to one). So, again, no effects of treatment presented.
Barnes maze: Data is presented in Fig. 5b and it is claimed that ‘the significant deficit in short-term memory retention in APPPS1 mice in the Barnes maze test was substantially ameliorated by icv treatment with p40-specific antibodies’. Here, the situation is reverse: results of pairwise group comparisons are indicated but no ANOVA analysis. And the conclusion on treatment effects is based on nothing else but “common sense” (i.e. ‘the enemy of my enemy is my friend’). In sum, no clear evidence presented that would support the claims made.
In addition, Supplementary Figure 9 may be worth a look as well: here, CNS p40 concentrations were analyzed in human samples to see whether previous findings in mice could be translated to humans with Alzheimer’s disease. For this purpose, p40 protein concentrations in cerebrospinal fluid specimens from diseased patients (n = 39) were compared to those from individuals without Alzheimer’s disease (n = 20). ‘A significant (p < 0.05) linear correlation of cognitive performance assessed by the mini-mental score evaluation (MMSE) with CSF p40 concentrations’ was found; however, instead of 59 data points as expected, Figure S9 only showed n=6 (control) and n=7 (AD) measurements, respectively, indicating that most individuals could not be included in this study – the p40 protein concentrations were simply below detection limit.
Nevertheless, we would like to emphasize that we are discussing this paper solely from the data analysis and presentation point of view and by no means we aim to challenge the scientific value of this paper that has been well cited and has triggered good-quality follow-up research.