Bacskai BJ, Hickey GA, Skoch J, Kajdasz ST, Wang Y, Huang GF, Mathis CA, Klunk WE, Hyman BT. Four-dimensional multiphoton imaging of brain entry, amyloid binding, and clearance of an amyloid-beta ligand in transgenic mice. Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12462-7. PubMed.

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  1. I think this is an excellent and exciting paper. Hopefully, direct imaging of AD pathology is just around the corner for patients. The compounds developed by Dr. Klunk and used by Dr. Hyman work extremely well for in-vivo two-photon work, and show promise in human PET studies. Up to now, imaging studies of AD pathology have used indirect methods that correlate various changes (entorhinal cortex volumes, 2DG-PET, etc.) to lesions. However, the development of methodologies that directly image lesions will be an important advance for both diagnosis and early treatment. We are working on developing ligands that could be used with magnetic resonance imaging, which has a better resolution than PET (see Wadghiri et al., 2003), and these methods also show promise.

    References:

    Wadghiri YZ, Sigurdsson EM, Sadowski M, Elliott JI, Li Y, Scholtzova H, Tang CY, Aguinaldo G, Pappolla M, Duff K, Wisniewski T, Turnbull DH. Detection of Alzheimer's amyloid in transgenic mice using magnetic resonance microimaging. Magn Reson Med. 2003 Aug;50(2):293-302. PubMed.

    View all comments by Thomas Wisniewski

  2. This is an extremely exciting paper, which reports outstanding work from the group of investigators in Pittsburgh and their collaborators around the world. There is considerable evidence that the protein called amyloid may play an important role in the development of Alzheimer's disease. The results shown in this paper are a major step forward in the development of tools to image amyloid in the human brain.

    The authors should be commended for their very careful step-by-step approach to the problem. Although considerably more work needs to be done in this area, this work is extremely promising for the development of a tool which could be used for diagnosis, monitoring the effects of treatment, and even possibly early detection of Alzheimer's disease.

    View all comments by Michael Weiner

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