Type 2 Diabetes and AD

Contributed by: Michael Rafii, M.D., Ph.D - Director of the Memory Disorders Clinic at the University of California, San Diego.
-----------------------------------

Patients with type 2 diabetes or "insulin resistant diabetes", particularly those who have poorly controlled blood sugar levels, are at a greater risk of developing AD. The reason for this is from a series of studies from Dennis Selkoe's group at Harvard Medical School. As readers of this blog will recall, beta amyloid is thought to accumulate in the brain of patients who develop AD.

An intriguing finding has been that beta amyloid is "broken down" in the brain by Insulin Degrading Enzyme. In patients with type 2 diabetes, the high insulin levels keep this enzyme too busy to break down the beta amyloid. When this occurs, the beta amyloid accumulates in the brain and leads to AD.

The good news is that by keeping blood sugars in check, the insulin levels will be lower, thus allowing the Insulin Degrading Enzyme to break down the harmful beta amyloid.

2 comments :

  1. What was the name of the study that this was taken from?

    Has there been any follow-up studies conducted?

    ReplyDelete
  2. Michael Rafii, MD, PhDJanuary 28, 2010 at 10:28 PM

    These are three important papers that demonstrate the interaction of IDE and Beta-amyloid. Further studies are underway.

    Kurochkin IV, Goto S (1994). "Alzheimer's beta-amyloid peptide specifically interacts with and is degraded by insulin degrading enzyme". FEBS Lett. 345 (1): 33–7

    Farris W, Mansourian S, Chang Y, Lindsley L, Eckman EA, Frosch MP, Eckman CB, Tanzi RE, Selkoe DJ, Guenette S (2003). "Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo". Proc. Natl. Acad. Sci. U.S.A. 100 (7): 4162–7.

    Kim M, Hersh LB, Leissring MA, Ingelsson M, Matsui T, Farris W, Lu A, Hyman BT, Selkoe DJ, Bertram L, Tanzi RE (2007). "Decreased catalytic activity of the insulin-degrading enzyme in chromosome 10-linked Alzheimer disease families". J. Biol. Chem. 282 (11): 7825–32.

    ReplyDelete