[P3–317]: DHA BRAIN UPTAKE AND APOE4 STATUS: A PET STUDY WITH [1‐¹¹C]‐DHA

Abstract

Background: The apolipoprotein E ɛ4 (APOE4) allele is the strongest genetic risk factor identified for developing Alzheimer's disease (AD). Among brain lipids, alteration in the ω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) homeostasis is implicated in AD pathogenesis. APOE4 may influence both brain DHA metabolism and cognitive outcomes. Methods: Using positron emission tomography, regional incorporation coefficients (k*), rates of DHA incorporation from plasma into the brain using [1-11 C]-DHA (J in ), and regional cerebral blood flow using [ 15 O]-water were measured in 22 middle-aged healthy adults (mean age 35 years, range 19-65 years). Data were partially volume error-corrected for brain atrophy. APOE4 phenotype was determined by protein expression, and unesterified DHA concentrations were quantified in plasma. An exploratory post hoc analysis of the effect of APOE4 on DHA brain kinetics was performed. Results: The mean global gray matter DHA incorporation coefficient, k*, was significantly higher (16%) among APOE4 carriers (n = 9) than among noncarriers (n = 13, p = 0.046). Higher DHA incorporation coefficients were observed in several brain regions, particularly in the entorhinal subregion, an area affected early in AD pathogenesis. Cerebral blood flow, unesterified plasma DHA, and whole brain DHA incorporation rate (J in ) did not differ significantly between the APOE groups.

Omega-3 PUFA metabolism and brain modifications during aging

“…In terms of PLs, Söderberg et al 116 found that the mean global gray matter DHA incorporation coefficient was 16% higher in APOE4 carriers vs non-carriers . A higher DHA incorporation coefficient was also observed in other regions including the entorhinal cortex 121 . However, the whole-brain DHA incorporation rate was not significantly different between APOE groups 121 .…”

“…A higher DHA incorporation coefficient was also observed in other regions including the entorhinal cortex 121 . However, the whole-brain DHA incorporation rate was not significantly different between APOE groups 121 . They also did not observe any age-related effects on DHA incorporation, but this may be due to the fact that only 4 of their 23 participants were over 50 years old 121 .…”

“…However, the whole-brain DHA incorporation rate was not significantly different between APOE groups 121 . They also did not observe any age-related effects on DHA incorporation, but this may be due to the fact that only 4 of their 23 participants were over 50 years old 121 . The authors hypothesized that increased DHA incorporation in the brains of APOE4 carriers could be a compensatory mechanism to counteract brain DHA loss 121 .…”

Aging, cognitive decline, apolipoprotein E and docosahexaenoic acid metabolism

“…Aldullah et al also reported a similar higher ARA: DHA ratio in PC and lyso-PC in hAPOE4 mice compared to hAPOE3 mice supporting that this mice model also have an imbalance in DHA and ARA compartment packaging (Abdullah et al, 2017). In ∼35 year-old humans, a positron emission tomography study with [1-11 C]-DHA reported however, that the mean global gray matter incorporation of DHA in the brain of E4 carriers was 16% higher than in non-carriers (Yassine et al, 2017). This higher uptake was particularly emphasized in the entorhinal region, an area affected early in AD pathogenesis and it was suggested by the authors it might represent a compensatory mechanism in younger E4 carriers to cope with increased brain DHA loss thus to maintain brain DHA levels (Yassine et al, 2017).…”

“…In ∼35 year-old humans, a positron emission tomography study with [1-11 C]-DHA reported however, that the mean global gray matter incorporation of DHA in the brain of E4 carriers was 16% higher than in non-carriers (Yassine et al, 2017). This higher uptake was particularly emphasized in the entorhinal region, an area affected early in AD pathogenesis and it was suggested by the authors it might represent a compensatory mechanism in younger E4 carriers to cope with increased brain DHA loss thus to maintain brain DHA levels (Yassine et al, 2017). Therefore, at younger ages, E4 carriers might require more DHA than non-carriers to support brain DHA turnover and prevent accumulation of Ab peptide since it was shown that higher plasma DHA levels were inversely associated to the brain Ab load (Yassine et al, 2016).…”