Omega-3
vetzuren in de strijd tegen Alzheimer*
Volgens een Amerikaans onderzoek beschermen omega-3
vetzuren tegen de ziekte van Alzheimer. Vooral het omega-3 vetzuur
Docosahexaeenzuur (DHA) stimuleert de
aanmaak van een eiwit. Een tekort van dit eiwit, LR11 doet de aanmaak van het
eiwit beta-amyloid stimuleren. Beta-amyloid is het belangrijkste bestanddeel van
de beschadigende plaques in de hersenen van Alzheimerpatiënten. De studie werd
uitgevoerd met celkweken van hersencellen, en in proefdieren die genetisch zo
waren veranderd dat ze Alzheimer ontwikkelen.
Omega-3 Fatty Acid Docosahexaenoic Acid Increases SorLA/LR11, a Sorting Protein
with Reduced Expression in Sporadic Alzheimer's Disease (AD): Relevance to AD
Prevention
Qiu-Lan Ma,1,3 Bruce Teter,1,3 Oliver J. Ubeda,1,3 Takashi Morihara,1,3,4
Dilsher Dhoot,1,3 Michael D. Nyby,1 Michael L. Tuck,1 Sally A. Frautschy,1,2,3
and Greg M. Cole1,2,3
Departments of 1Medicine and 2Neurology, University of California, Los Angeles,
California 90095, 3Geriatric Research, Education and Clinical Center, Veterans
Affairs, Greater Los Angeles Healthcare System, North Hills, California 91343,
and 4Department of Post-Genomics and Diseases, Division of Psychiatry and
Behavioral Proteomics, Osaka University Graduate School of Medicine D3,
Suita-shi, Osaka 565-0871, Japan
Correspondence should be addressed to Greg M. Cole, Veterans Affairs, Greater
Los Angeles Healthcare System Research 151, Building 7, Room A101, 16111 Plummer
Street, North Hills, CA 91343. Email: gmcole@ucla.edu
Environmental and genetic factors, notably ApoE4, contribute to the etiology of
late-onset Alzheimer's disease (LOAD). Reduced mRNA and protein for an
apolipoprotein E (ApoE) receptor family member, SorLA (LR11) has been found in
LOAD but not early-onset AD, suggesting that LR11 loss is not secondary to
pathology. LR11 is a neuronal sorting protein that reduces amyloid precursor
protein (APP) trafficking to secretases that generate β-amyloid (Aβ).
Genetic polymorphisms that reduce LR11 expression are associated with increased
AD risk. However these polymorphisms account for only a fraction of cases with
LR11 deficits, suggesting involvement of environmental factors. Because
lipoprotein receptors are typically lipid-regulated, we postulated that LR11 is
regulated by docosahexaenoic acid (DHA), an essential -3 fatty acid related to
reduced AD risk and reduced Aβ accumulation. In this study, we report that
DHA significantly increases LR11 in multiple systems, including primary rat
neurons, aged non-Tg mice and an aged DHA-depleted APPsw AD mouse model. DHA
also increased LR11 in a human neuronal line. In vivo elevation of LR11 was also
observed with dietary fish oil in young rats with insulin resistance, a model
for type II diabetes, another AD risk factor. These data argue that DHA
induction of LR11 does not require DHA-depleting diets and is not age dependent.
Because reduced LR11 is known to increase Aβ production and may be a
significant genetic cause of LOAD, our results indicate that DHA increases in
SorLA/LR11 levels may play an important role in preventing LOAD. (December 2007)
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