Abstract
Lower levels of the cognitively beneficial docosahexaenoic acid (DHA) are often observed in Alzheimer's disease (AD) brains. Brain DHA levels are regulated by the blood-brain barrier (BBB) transport of plasma-derived DHA, a process facilitated by fatty acid-binding protein 5 (FABP5). This study reports a 42.1 ± 12.6% decrease in the BBB transport of 14C-DHA in 8-month-old AD transgenic mice (APPswe,PSEN1∆E9) relative to wild-type mice, associated with a 34.5 ± 6.7% reduction in FABP5 expression in isolated brain capillaries of AD mice. Furthermore, short-term spatial and recognition memory deficits were observed in AD mice on a 6-month n-3 fatty acid-depleted diet, but not in AD mice on control diet. This intervention led to a dramatic reduction (41.5 ± 11.9%) of brain DHA levels in AD mice. This study demonstrates FABP5 deficiency and impaired DHA transport at the BBB are associated with increased vulnerability to cognitive deficits in mice fed an n-3 fatty acid-depleted diet, in line with our previous studies demonstrating a crucial role of FABP5 in BBB transport of DHA and cognitive function.
| Original language | English |
|---|---|
| Pages (from-to) | 81-92 |
| Number of pages | 12 |
| Journal | Journal of Neurochemistry |
| Volume | 144 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1 Jan 2018 |
Keywords
- Alzheimer's disease
- blood-brain barrier
- cognitive function
- docosahexaenoic acid
- fatty acid-binding protein
- omega-3 fatty acids
Cite this
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Reduced blood-brain barrier expression of fatty acid-binding protein 5 is associated with increased vulnerability of APP/PS1 mice to cognitive deficits from low omega-3 fatty acid diets. / Pan, Yijun; Choy, Kwok H.C.; Marriott, Philip J.; Chai, Siew Y.; Scanlon, Martin J.; Porter, Christopher J.H.; Short, Jennifer L.; Nicolazzo, Joseph A.
In: Journal of Neurochemistry, Vol. 144, No. 1, 01.01.2018, p. 81-92.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Reduced blood-brain barrier expression of fatty acid-binding protein 5 is associated with increased vulnerability of APP/PS1 mice to cognitive deficits from low omega-3 fatty acid diets
AU - Pan, Yijun
AU - Choy, Kwok H.C.
AU - Marriott, Philip J.
AU - Chai, Siew Y.
AU - Scanlon, Martin J.
AU - Porter, Christopher J.H.
AU - Short, Jennifer L.
AU - Nicolazzo, Joseph A.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Lower levels of the cognitively beneficial docosahexaenoic acid (DHA) are often observed in Alzheimer's disease (AD) brains. Brain DHA levels are regulated by the blood-brain barrier (BBB) transport of plasma-derived DHA, a process facilitated by fatty acid-binding protein 5 (FABP5). This study reports a 42.1 ± 12.6% decrease in the BBB transport of 14C-DHA in 8-month-old AD transgenic mice (APPswe,PSEN1∆E9) relative to wild-type mice, associated with a 34.5 ± 6.7% reduction in FABP5 expression in isolated brain capillaries of AD mice. Furthermore, short-term spatial and recognition memory deficits were observed in AD mice on a 6-month n-3 fatty acid-depleted diet, but not in AD mice on control diet. This intervention led to a dramatic reduction (41.5 ± 11.9%) of brain DHA levels in AD mice. This study demonstrates FABP5 deficiency and impaired DHA transport at the BBB are associated with increased vulnerability to cognitive deficits in mice fed an n-3 fatty acid-depleted diet, in line with our previous studies demonstrating a crucial role of FABP5 in BBB transport of DHA and cognitive function.
AB - Lower levels of the cognitively beneficial docosahexaenoic acid (DHA) are often observed in Alzheimer's disease (AD) brains. Brain DHA levels are regulated by the blood-brain barrier (BBB) transport of plasma-derived DHA, a process facilitated by fatty acid-binding protein 5 (FABP5). This study reports a 42.1 ± 12.6% decrease in the BBB transport of 14C-DHA in 8-month-old AD transgenic mice (APPswe,PSEN1∆E9) relative to wild-type mice, associated with a 34.5 ± 6.7% reduction in FABP5 expression in isolated brain capillaries of AD mice. Furthermore, short-term spatial and recognition memory deficits were observed in AD mice on a 6-month n-3 fatty acid-depleted diet, but not in AD mice on control diet. This intervention led to a dramatic reduction (41.5 ± 11.9%) of brain DHA levels in AD mice. This study demonstrates FABP5 deficiency and impaired DHA transport at the BBB are associated with increased vulnerability to cognitive deficits in mice fed an n-3 fatty acid-depleted diet, in line with our previous studies demonstrating a crucial role of FABP5 in BBB transport of DHA and cognitive function.
KW - Alzheimer's disease
KW - blood-brain barrier
KW - cognitive function
KW - docosahexaenoic acid
KW - fatty acid-binding protein
KW - omega-3 fatty acids
UR - http://www.scopus.com/inward/record.url?scp=85038258541&partnerID=8YFLogxK
U2 - 10.1111/jnc.14249
DO - 10.1111/jnc.14249
M3 - Article
C2 - 29105065
AN - SCOPUS:85038258541
VL - 144
SP - 81
EP - 92
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 1
ER -