Document Detail


Deficient liver biosynthesis of docosahexaenoic acid correlates with cognitive impairment in Alzheimer's disease.
MedLine Citation:
PMID:  20838618     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Reduced brain levels of docosahexaenoic acid (C22:6n-3), a neurotrophic and neuroprotective fatty acid, may contribute to cognitive decline in Alzheimer's disease. Here, we investigated whether the liver enzyme system that provides docosahexaenoic acid to the brain is dysfunctional in this disease. Docosahexaenoic acid levels were reduced in temporal cortex, mid-frontal cortex and cerebellum of subjects with Alzheimer's disease, compared to control subjects (P  =  0.007). Mini Mental State Examination (MMSE) scores positively correlated with docosahexaenoic/α-linolenic ratios in temporal cortex (P =  0.005) and mid-frontal cortex (P  =  0.018), but not cerebellum. Similarly, liver docosahexaenoic acid content was lower in Alzheimer's disease patients than control subjects (P  =  0.011). Liver docosahexaenoic/α-linolenic ratios correlated positively with MMSE scores (r  =  0.78; P<0.0001), and negatively with global deterioration scale grades (P  =  0.013). Docosahexaenoic acid precursors, including tetracosahexaenoic acid (C24:6n-3), were elevated in liver of Alzheimer's disease patients (P  =  0.041), whereas expression of peroxisomal d-bifunctional protein, which catalyzes the conversion of tetracosahexaenoic acid into docosahexaenoic acid, was reduced (P  = 0.048). Other genes involved in docosahexaenoic acid metabolism were not affected. The results indicate that a deficit in d-bifunctional protein activity impairs docosahexaenoic acid biosynthesis in liver of Alzheimer's disease patients, lessening the flux of this neuroprotective fatty acid to the brain.
Authors:
Giuseppe Astarita; Kwang-Mook Jung; Nicole C Berchtold; Vinh Q Nguyen; Daniel L Gillen; Elizabeth Head; Carl W Cotman; Daniele Piomelli
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-09-08
Journal Detail:
Title:  PloS one     Volume:  5     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2010  
Date Detail:
Created Date:  2010-09-14     Completed Date:  2011-02-18     Revised Date:  2013-07-24    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e12538     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, University of California Irvine, Irvine, California, United States of America.
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MeSH Terms
Descriptor/Qualifier:
Aged
Aged, 80 and over
Alzheimer Disease / metabolism*,  psychology*
Brain / metabolism
Case-Control Studies
Cognition*
Docosahexaenoic Acids / deficiency*
Female
Humans
Liver / metabolism*
Male
Neuropsychological Tests
Grant Support
ID/Acronym/Agency:
P01 AG00538/AG/NIA NIH HHS; P30 AG19610/AG/NIA NIH HHS; P50 AG016573/AG/NIA NIH HHS; R01 DA012447/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
25167-62-8/Docosahexaenoic Acids
Comments/Corrections

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