Morales-Corraliza J, Wong H, Mazzella MJ, Che S, Lee SH, Petkova E, Wagner JD, Hemby SE, Ginsberg SD, Mathews PM. Brain-Wide Insulin Resistance, Tau Phosphorylation Changes, and Hippocampal Neprilysin and Amyloid-β Alterations in a Monkey Model of Type 1 Diabetes. J Neurosci. 2016 Apr 13;36(15):4248-58. PubMed.

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  1. I really like this paper because it demonstrates, in a primate model, that STZ-diabetes causes molecular/biochemical abnormalities that are characteristic of AD and strengthens the hypothesis that AD is a variant of diabetes mellitus (DM). This work represents a continuation of the story in which similar findings were reported in rat and I believe also mouse models. A few things missing from the work raise questions. What was the neuropathology in these monkeys? Did they have any cognitive or behavioral abnormalities? Did they have any vascular amyloid? And did authors exclude the possibility that STZ crossed the blood-brain barrier and directly caused CNS disease? The point about intracerebroventricular STZ is to show that even without type 1 (T1DM) or type 2 diabetes (T2DM), exactly the same abnormalities seen in AD can be produced. The bigger question raised by our group some time ago is, what is the link between STZ and AD? High fat/caloric diets produce T2DM, but brain abnormalities, although similar to AD, are not as severe. In addition, individuals with T1DM get cognitive impairment, but not with the severity seen in STZ models. In other words, I believe this paper helps greatly in supporting the overall concept but also indicates the need to dig deeper into the specific mechanisms of disease. For example, the authors didn't address the role of inflammation, which is part of DM and an early abnormality in AD.

    View all comments by Suzanne de la Monte

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