Document Detail

Vascular nitric oxide, sex hormone replacement, and fish oil may help to prevent Alzheimer's disease by suppressing synthesis of acute-phase cytokines.
MedLine Citation:
PMID:  10616034     Owner:  NLM     Status:  MEDLINE    
The neurodegenerative plaques of Alzheimer's disease (AD) are characterized by a self-sustaining acute-phase reaction in which both interleukin-1 (IL-1) and interleukin-6 (IL-6) are up-regulated. The fact that IL-6 is detectable in early stage diffuse plaques encourages the speculation that the acute-phase process is crucial to the pathogenesis of AD. The epidemiological association of AD with estrogen deficiency, as well as with various disorders characterized by vascular endotheliopathy, suggest a protective role for vascular nitric oxide (NO). NO has an autocrine anti-inflammatory impact on endothelium, owing in part to antagonism of NF-kappaB activity; since induction of IL-6 is dependent on NF-kappaB, this may explain recent evidence that NO inhibits macrophage IL-6 production. It is reasonable to postulate that, analogously, cerebrovascular NO decreases IL-6 production in the brain. Vascular NO may also have direct neuroprotective activity. Estrogen, in addition to promoting vascular NO synthesis, can block IL-6 production by a more direct mechanism in cells expressing estrogen receptors; since such receptors have been reported in brain glia and astrocytes, estrogen has the potential to limit brain IL-1 activity. Testosterone likewise can inhibit IL-6 induction in androgen-responsive cells, which may include brain glia and astrocytes. Since fish oil and gamma linolenic acid (GLA) suppress IL-1 production by stimulated monocytes, they conceivably could exert this effect in the brain as well; the comparatively low prevalence of AD in elderly Japanese is intriguing in this regard. These considerations suggest that a healthy cerebrovascular endothelium, sex hormone activity, and dietary fish oil/GLA may slow or prevent AD onset by dampening acute-phase mechanisms in the brain.
M F McCarty
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Medical hypotheses     Volume:  53     ISSN:  0306-9877     ISO Abbreviation:  Med. Hypotheses     Publication Date:  1999 Nov 
Date Detail:
Created Date:  2000-01-20     Completed Date:  2000-01-20     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  7505668     Medline TA:  Med Hypotheses     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  369-74     Citation Subset:  IM    
Nutrition 21/AMBI, San Diego, CA, USA.
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MeSH Terms
Alzheimer Disease / prevention & control*
Blood Vessels / metabolism
Dihydrotestosterone / administration & dosage,  pharmacology
Down-Regulation / drug effects
Estradiol / administration & dosage,  pharmacology
Fish Oils / pharmacology,  therapeutic use*
Hormone Replacement Therapy*
Interleukin-1 / antagonists & inhibitors*,  biosynthesis
Interleukin-6 / antagonists & inhibitors*,  biosynthesis
Nitric Oxide / physiology*
Reg. No./Substance:
0/Fish Oils; 0/Interleukin-1; 0/Interleukin-6; 10102-43-9/Nitric Oxide; 50-28-2/Estradiol; 521-18-6/Dihydrotestosterone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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