. Glycogen synthase kinase-3 is increased in white cells early in Alzheimer's disease. Neurosci Lett. 2005 Jan 3;373(1) PubMed.


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  1. This paper adds an important molecule to the list of molecules found to be affected in peripheral cells in AD, and is consistent with a suggestion that AD is a systemic disease.

  2. Peripheral Diagnosis of Signaling Intermediates in Alzheimer Disease
    The need for accurate diagnostics in Alzheimer disease is one of the most pressing issues in the field today, and this is especially true for diagnostic tools, which employ easily attainable biological samples such as blood. Due to the apparent involvement of GSK-3 in both amyloid processing and tau phosphorylation as well as its expression in a number of diverse tissues, most notably, in this case circulating lymphocytes, GSK-3 is rapidly becoming a leading candidate as a diagnostic tool for Alzheimer disease. The finding of increased expression and activation of GSK-3 in MCI cases, but not in age-matched control cases, offers further support for the role of GSK-3 as a diagnostic tool for the early detection of Alzheimer disease (Hy et al., 2005). While this study focuses solely on the diagnostic potential of GSK-3 in Alzheimer disease, this same rationale also supports the diagnostic potential of other widely expressed cell signaling molecules known to play an early role in the pathogenesis of Alzheimer disease, including members of the MAPK pathway, such as ERK and JNK (Perry et al., 1999; Zhu et al., 2001a,b, 2004).

    Kate M. Webber, Mark A. Smith, Xiongwei Zhu, George Perry Institute of Pathology, Case Western Reserve University, Cleveland, Ohio


    . Glycogen synthase kinase-3 is increased in white cells early in Alzheimer's disease. Neurosci Lett. 2005 Jan 3;373(1) PubMed.

    . Activation of neuronal extracellular receptor kinase (ERK) in Alzheimer disease links oxidative stress to abnormal phosphorylation. Neuroreport. 1999 Aug 2;10(11):2411-5. PubMed.

    . Differential activation of neuronal ERK, JNK/SAPK and p38 in Alzheimer disease: the 'two hit' hypothesis. Mech Ageing Dev. 2001 Dec;123(1):39-46. PubMed.

    . Activation and redistribution of c-jun N-terminal kinase/stress activated protein kinase in degenerating neurons in Alzheimer's disease. J Neurochem. 2001 Jan;76(2):435-41. PubMed.

    . Alzheimer's disease: the two-hit hypothesis. Lancet Neurol. 2004 Apr;3(4):219-26. PubMed.

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  1. GSK-3—A Peripheral Marker for AD?