Journal
JOURNAL OF NEUROSCIENCE
Volume 27, Issue 52, Pages 14299-14307Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3593-07.2007
Keywords
sorLA; LR11; Alzheimer; docosahexaenoic acid; diet; omega-3 fatty acid; amyloid
Categories
Funding
- NCCIH NIH HHS [AT3008, R01 AT003008-01, R01 AT003008-03, R01 AT003008, R01 AT003008-02] Funding Source: Medline
- NIA NIH HHS [R01 AG013741-08, R01 AG013741, P50 AG016570-100005, R01 AG021975-04, R01 AG021975-03, P50 AG016570, AG13471, R01 AG013741-07A2, P50 AG016570-090005, R01 AG021975] Funding Source: Medline
Ask authors/readers for more resources
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 beta-amyloid (A beta). 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 omega-3 fatty acid related to reduced AD risk and reduced A beta 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 A beta 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available