The Durk Pearson & Sandy Shaw^®
Life Extension News^TM
Volume 5 No. 6 • December 2002

Neuroprotection, IGF-1, and Alzheimer’s Disease

A new paper in Nature Medicine¹ reports that serum IGF-1 regulates brain amyloid-beta levels. This is a hitherto unreported effect of IGF-1, though it has been known that IGF-1 is required for the neuroprotective effects of exercise on the brain and that it modulates adult neurogenesis and increases neuronal excitability.¹

As the authors note, insulin is known to modulate cellular clearance of amyloid-beta, and IGF-1 protects neurons against amyloid-beta’s toxic effects. In exploring the effect of IGF-1 on brain amyloid-beta levels, the researchers used aged (over 18 months) rats that already had elevated levels of amyloid-beta in the brain, and compared them to young rats. They found that IGF-1 treatment caused amyloid-beta levels in the hippocampus and cortex of the aging rats to decrease to those seen in young rats. Gliosis (the proliferation of brain glial cells) seen with aging was “eradicated.”

The researchers found that the transport of labeled albumin from the bloodstream into the cerebrospinal fluid (CSF) was greatly enhanced with IGF-1 treatment. Hence, they hypothesize that this might explain the increased amyloid-beta clearance, since amyloid-beta might be transported out of the brain by albumin, to which it is known to bind, or by other serum proteins.

The other particularly interesting finding in this study is that TNF-alpha (tumor necrosis factor-alpha, an inflammatory cytokine) antagonized the stimulatory effects of IGF-1 on amyloid-beta clearance. This is just another good reason to reduce fat stores. Fat cells (adipocytes) are known to synthesize and release TNF-alpha into the circulation. Substances known to suppress TNF-alpha include nonsteroidal anti-inflammatory drugs (NSAIDs),² estrogen,³ alpha-lipoic acid,⁴ resistance exercise,⁵ quercetin,⁶ N-acetylcysteine, thalidomide, and pentoxifylline.

References

1. Carro et al. Serum insulin-like growth factor 1 regulates brain amyloid-beta levels. Nature Med 8(12):1390-7 (2002).
2. Joussen et al. Nonsteroidal anti-inflammatory drugs prevent early diabetic retinopathy via TNF-alpha suppression. FASEB J (Jan. 30, 2002).
3. Cenci et al. Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-alpha. J Clin Invest 106(10):1229-37 (2000). Walsh et al. 17-beta-Estradiol reduces tumor necrosis factor-alpha-mediated LDL accumulation in the artery wall. J Lipid Res 40:387-96 (1999).
4. Zhang, Frei. Alpha-lipoic acid inhibits TNF-alpha-induced NF-kappaB activation and adhesion molecule expression in human aortic endothelial cells. FASEB J 15:2423-32 (2001).
5. Greiwe et al. Resistance exercise decreases skeletal muscle tumor necrosis factor alpha in frail elderly humans. FASEB J 15:475-82 (2001).
6. Wang, Mazza. Effects of anthocyanins and other phenolic compounds on the production of tumor necrosis factor alpha in LPS/IFN-gamma-activated RAW 264.7 macrophages. J Agric Food Chem 50:4183-9 (2002).