Higher intake of fatty, cold-water fish (such as tuna, salmon, and mackerel) has long been associated with a lower risk of dementia and Alzheimer's and epidemiological studies suggest that dietary supplements of omega-3 polyunsaturated fatty acids might also protect against Alzheimer's disease. Little is known though about how this protection might arise and whether such supplements might really help Alzheimer's patients or those at genetic risk for the disease.
A new study by Greg Cole and his colleagues have shed considerable light on this protective mechanism. They say that their findings in mice show how Alzheimer's patients seem to be caught in a vicious circle, with their disease accelerating the loss of such essential fatty acids, making dietary supplements especially important.
In their studies, the researchers tested the effects of dietary depletion or enhancement of the essential fatty acid docosahexaenoic acid (DHA) on transgenic mice engineered to have the human version of a mutant amyloid precursor protein (APP)--the source of the brain-clogging protein in Alzheimer's disease.
The researchers' analyses revealed that such animals showed particular vulnerability to damage to structural proteins that make up the "receiving stations"--called dendrites--on neurons in their brains. These dendrites, mushroom-shaped structures that festoon the surfaces of neurons, take in chemical signals from neighboring neurons to trigger nerve impulses. Dendrites are located on the "postsynaptic," or receiving, side of the connections between neurons, known as synapses. The dendritic proteins are damaged by oxidation chemical reactions, which the antioxidant DHA is known to protect against.
When the researchers restricted dietary fatty acids in the transgenic mice, they detected a decreased level of DHA in the brains of the transgenic animals compared to normal mice. They also detected a comparative increase in damage to the dendrites, and they saw evidence that reduced DHA caused increased "oxidative stress" in the transgenic animals, which could cause damage. When they supplemented the animals with DHA, however, they found a protection against such damage.
In behavioral studies, the researchers also found that the transgenic mice on low-DHA diets showed "profound performance deficits" in learning and remembering the location of hidden, submerged platforms in a tank called the Morris water maze. Supplementing the mice with DHA, however, prevented this deficit.
"The present results provide, for the first time, evidence that the combination of genetic (mutant human APP) and environmental risk factors (dietary essential fatty acids) for AD can act synergistically to quantitatively reduce synaptic proteins, specifically, dendritic scaffold proteins, that are critical for cognition as evidenced by memory deficits observed in the Morris water maze paradigm," wrote the researchers.
"The results show a dramatic impact of diet on the expression of the AD-related postsynaptic marker phenotype and provide new insight into how essential fatty acid intake may modulate the expression of neurodegenerative diseases, including AD," they wrote.
The researchers also wrote that their findings "suggest that patients bearing a genetic risk of AD may be more vulnerable to a lack of essential fatty acids," which tend to be reduced in the brain both in normal aging and AD. They concluded that their findings "support the idea that increased DHA intake should be considered as a potential neuroprotective strategy for AD."