Abstract
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.
Document Type
Article
Publication Date
9-8-2010
Digital Object Identifier (DOI)
http://dx.doi.org/10.1371/journal.pone.0012538
Repository Citation
Astarita, Giuseppe; Jung, Kwang-Mook; Berchtold, Nicole C.; Nguyen, Vinh Q.; Gillen, Daniel L.; Head, Elizabeth; Cotman, Carl W.; and Piomelli, Daniele, "Deficient liver biosynthesis of docosahexaenoic acid correlates with cognitive impairment in Alzheimer's disease" (2010). Sanders-Brown Center on Aging Faculty Publications. 13.
https://uknowledge.uky.edu/sbcoa_facpub/13
Supporting documents
Notes/Citation Information
Published in PLoS ONE, v. 5, no. 9, e12538.
© 2010 Astarita et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.