Ageing-associated decline, especially cognitive decline, is a social-medical condition that would directly affect overall societal wellbeing. It is still widely unmet biomedical challenge. In general, medical conditions related to brain functions are the least understood topics in medicine.
Recently journal Nature Medicine has published an article suggesting that high level of β2-microglobulin, a component of immune system class I antigen-presentation pathway, correlated to cognitive decline during ageing.
These is a mouse study. Now, this is a big caveat. In addition, though the authors believe they studied "cognitive" function in mice, the actual experiments, in my view, are based more on mouse locomotor skills.
Initially, the authors reported that both in mice or humans ageing correlated with increased level of β2-microglobulin in the circulation.
Next, the authors showed that young 3 months old mice intravenously injected with β2-microglobulin made more errors in tasks requiring locomotor skills (water maze and fear freeze).
Interestingly, this negative effect of exogenous β2-microglobulin on mouse locomotive skills were short-lived (< 30 days, see d).
Importantly, β2-microglobulin-injected young TAP1 KO mice that lack surface MHC class I molecules did not show decline in their locomotive skills.
Finally, old (17 months) β2-microglobulin KO mice showed less errors in their locomotive skills compared to their wild-type littermates.
In summary, this study claims that increase in β2-microglobulin level may indicate in locomotive skills in mice. Now, there are some major weakness in this paper that could affect its validity: (1) β2-microglobulin is a ~12kD size molecule that would have hard time to cross brain blood barrier (BBB); (2) there is substantial overlap between baseline and experimental errors in young mice in different figures (compare Fig. 1e vs. Fig. 2c vs. Fig. 4a); (3) outcome of experiments with β2-microglobulin injection into young β2-microglobulin KO are not done or not shown.
David Usharauli
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