. Increased T cell reactivity to amyloid beta protein in older humans and patients with Alzheimer disease. J Clin Invest. 2003 Aug;112(3):415-22. PubMed.

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  1. Although it is true that immune response, and the resulting higher levels of selective immunoglobulins, are present in AD, this can only (and at best) imply immune system components. We cannot jump the gun on proposing an autoimmune response. It may be wiser to hypothesize that inflammation is a result of (not genesis of) Alzheimer's disease.

    Furthermore, I did not see enough relevant research on ligand binding as an underlying cause of overaccumulation of amyloid beta protein or the link between genectics and amyloid precursor protein.

  2. This is a very good paper for increased T cell reactivity in Alzheimer disease, but the authors failed to refer to previous research, including our own report of abnormal lymphocyte proliferation by amyloid protein-β in AD patients (Singh, 1994). I wish people would read up on the previous literature on faulty immune regulation and autoimmunity in AD (Singh, 1997).

    Dr. Jacob Mack's point might be well taken, but the most important thing is the "immune activation" that precedes inflammation and/or autoimmunity. Both are directly relevant to a cell-mediated autoimmune mechanism of pathogenesis in AD, which we proposed previously (see reference below). And Dr. Howard Weiner's group is now finding experimental evidence in favor of this hypothesis. Unfortunately, because nobody was giving us funding, we had to stop working on the immunopathogenesis of AD. So, I convey my heartfelt good wishes to those who are continuing immunology-autoimmunity research in AD, especially since nobody knows what causes AD.

    To that end, thinking outside the box would help us find some new clues.

    References:

    . Studies of neuroimmune markers in Alzheimer's disease. Mol Neurobiol. 1994 Aug-Dec;9(1-3):73-81. PubMed.

    . Immune-activation model in Alzheimer disease. Mol Chem Neuropathol. 1996 May-Aug;28(1-3):105-11. PubMed.

    . Neuroautoimmunity: pathogenic implications for Alzheimer's disease. Gerontology. 1997;43(1-2):79-94. PubMed.