Connecting Alzheimer’s, Cardiovascular Disease, Parkinson’s Disease, and Type 2 Diabetes

The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 7 No. 3 • June 2004

Connecting Alzheimer’s, Cardiovascular Disease, Parkinson’s Disease, and Type 2 Diabetes

It has become well known among those keeping up with scientific work on Alzheimer’s that the disease involves abnormal aggregated clumps of a normal protein, the infamous beta-amyloid protein. Less well known, perhaps, is that Parkinson’s disease involves abnormal aggregated clumps of another protein, alpha-synuclein, and that type 2 diabetes involves abnormal aggregated clumps of a different protein, amylin. Other examples are the prion proteins associated with variant Creutzfeldt-Jakob and mad cow disease. Recently, an aggregated protein with a similar structure (called an amyloid fibril) that is formed from clumped apolipoprotein C-II was reported in atherosclerotic plaques.1

What all these abnormal aggregations have in common is not chemical composition, but a chemical structure called fibrils. Fibrils are structures formed by proteins misfolded in such a way that they become insoluble and inclined to clump together, forming abnormal aggregations that are difficult to remove. As is becoming clear, many proteins are susceptible to this type of misfolding, and the misfolding (of at least some proteins) becomes more common with age. The researchers who found the clumped apolipoprotein C-II in atherosclerotic plaques had previously reported that the scavenger receptor CD36 initiates a signaling cascade upon binding to fibrillar beta-amyloid in the brain that causes the recruitment of microglia (immune cells in the brain) and the production of inflammatory mediators. Now they find that the fibrillar apolipoprotein C-II induces a CD36 signaling cascade in human atheroma that they believe may promote atherogenesis.

In another paper,2 the authors note that “There is increasing evidence that fibrillar aggregates are not esoteric species associated with a small number of proteins, but instead are a generic form of polypeptide structure that results from the dominance of interactions involving the main chain common to all such molecules.”

Other researchers report finding CD36 to be highly expressed in the cerebral cortex of Alzheimer’s patients and in cognitively normal aged individuals with diffuse amyloid plaques (as compared to age-matched individuals without amyloid plaques).3 Interestingly, a number of substances have been shown to decrease expression of CD36, including vitamin E,4 corticosteroids, TGF-beta1 (transforming growth factor-beta1), and HDL (another good reason to have high HDL levels!).5

  1. Medeiros et al. Fibrillar amyloid protein present in atheroma activates CD36 signal transduction. J Biol Chem 279(11):10643-8 (2004).
  2. Dobson. In the footsteps of alchemists. Science 304:1259-62 (2004).
  3. Ricciarelli et al. CD36 overexpression in human brain correlates with beta-amyloid deposition but not with Alzheimer’s disease. Free Rad Biol Med 36(8):1018-24 (2004).
  4. Devaraj et al. Alpha-tocopherol decreases CD36 expression in human monocyte-derived macrophages. J Lipid Res 42:521-7 (2001).
  5. Febbraio et al. CD36: a class B scavenger receptor involved in angiogenesis, atherosclerosis, inflammation, and lipid metabolism. J Clin Investig 108(6):785-91 (2001).

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