Fatty acid facts, Part IV: docosahexaenoic acid and Alzheimer's disease. A story of mice, men and fish.
The primary pathological hallmark of Alzheimer's disease (AD) is neurodegeneration by neuronal cell death caused by the development of aggregates of beta- amyloid peptide. Epidemiologically, low fish intake and low blood levels of the omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) have been related to an increased risk of AD. Test animals on dietary DHA depletion show learning and memory deficits, whereas their brains show inflammatory and oxidative damage to neurons and synaptic defects. The behavioral defects could be reversed by DHA supplementation exemplified by improved cognitive function. Mechanistically, these phenomena have been explained by the antiinflammatory action of DHA. This immunomodulation has been ascribed to incorporation of increased amounts of DHA in cell membrane phospholipids, leading to decreased production of proinflammatory omega-6 eicosanoids. The latter molecules may cause vascular damage which promotes the clinical signs of AD. This review will provide an overview on the available knowledge with regard to the role of DHA in AD with a focus on mechanistic and epidemiological investigations.
Pauwels
Ernest K J
EK
Leiden University Medical Center, Leiden, the Netherlands; Dept. Nuclear Medicine, Pisa University Medical School, Pisa, Italy. ernestpauwels@gmail.com
Volterrani
Duccio
D
Mariani
Giuliano
G
Kairemo
Kalevi
K
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002986:Clinical Trials as Topic; D004281:Docosahexaenoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology / Q000627:therapeutic use*; D005399:Fishes; D006801:Humans; D051379:Mice; D017747:Seafood
D015525:Fatty Acids, Omega-3; D004281:Docosahexaenoic Acids