The APP and AP in AD is a good topic, but some important issues are not being investigated. I think the autoimmune response to AP is important but not investigated. Many years ago (as early as 1985), I advanced the "Autoimmune Hypothesis and Immunotherapy for AD," and even showed a significant increase of antibodies to AP-β in sera of AD patients (Singh, 1990 and Singh, 1997).

This finding has recently been replicated by others (Mruthini et al., 2004). Although these researchers did not even cite our work, I would like to emphasize the importance of this line of investigation for immunotherapy. We need to examine the potential of immune modulation therapy (IMT) and not just the antiinflammatory drugs as a treatment for AD patients.

View all comments by Vijendra Singh

To cure Alzheimer disease, we need to understand the basic mechanism of cell death, which has remained elusive until now.

Almost all the drugs used in clnical trials like sex hormones, NSAIDs, and androgens affect one or more carbonic anhydrase isozymes, but are not sufficient to treat the disease because these trials do not assay the level of carbonic anhydrase isozymes that are reduced during aging and disorders including Alzheimer disease and other neurodegenerative diseases.

Understanding APP and Aβ function could help, but not cure AD.

See U.S. Patent # 6821997 issued November 23,2004 which can be viewed at http://www.uspto.gov "Therapeutic and Prophylactic Treatment of Aging and Disorders of Aging in Humans" by Victorio C. Rodriguez M.D.

View all comments by Victorio Rodriguez

I agree with this comment. We could analyze APP and Aβ until we are blue in the face, but the point now is to take what we know about AD and propose new and ingenious treatment modalities.

Gene therapy certainly is not going to do it and neither is immunotherapy. NSAIDS show some preventive roles, but will not regress AD. Turn off every complement protein (c reactive protein signaler, etc.) and we still have AD, just not less progressive; try to destroy beta amyloid and you destroy neurons and activate glial cells. We have a very powerful positive feedback loop here. It is necessary to cut the chains that initiate and propagate neuronal degradation.

View all comments by Jacob Mack