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Dietary DHA supplementation in an APP/PS1 transgenic rat model of AD reduces behavioral and A? pathology and modulates A? oligomerization.

ABSTRACT: Increased dietary consumption of docosahexaenoic acid (DHA) is associated with decreased risk for Alzheimer's disease (AD). These effects have been postulated to arise from DHA's pleiotropic effects on AD pathophysiology, including its effects on ?-amyloid (A?) production, aggregation, and toxicity. While in vitro studies suggest that DHA may inhibit and reverse the formation of toxic A? oligomers, it remains uncertain whether these mechanisms operate in vivo at the physiological concentrations of DHA attainable through dietary supplementation. We sought to clarify the effects of dietary DHA supplementation on A? indices in a transgenic APP/PS1 rat model of AD. Animals maintained on a DHA-supplemented diet exhibited reductions in hippocampal A? plaque density and modest improvements on behavioral testing relative to those maintained on a DHA-depleted diet. However, DHA supplementation also increased overall soluble A? oligomer levels in the hippocampus. Further quantification of specific conformational populations of A? oligomers indicated that DHA supplementation increased fibrillar (i.e. putatively less toxic) A? oligomers and decreased prefibrillar (i.e. putatively more toxic) A? oligomers. These results provide in vivo evidence suggesting that DHA can modulate A? aggregation by stabilizing soluble fibrillar A? oligomers and thus reduce the formation of both A? plaques and prefibrillar A? oligomers. However, since fibrillar A? oligomers still retain inherent neurotoxicity, DHA may need to be combined with other interventions that can additionally reduce fibrillar A? oligomer levels for more effective prevention of AD in clinical settings.

SUBMITTER: Teng E

PROVIDER: S-EPMC4641021 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Dietary DHA supplementation in an APP/PS1 transgenic rat model of AD reduces behavioral and Aβ pathology and modulates Aβ oligomerization.

Teng Edmond E Taylor Karen K Bilousova Tina T Weiland David D Pham Thaidan T Zuo Xiaohong X Yang Fusheng F Chen Ping-Ping PP Glabe Charles G CG Takacs Alison A Hoffman Dennis R DR Frautschy Sally A SA Cole Gregory M GM

Neurobiology of disease 20150912

Increased dietary consumption of docosahexaenoic acid (DHA) is associated with decreased risk for Alzheimer's disease (AD). These effects have been postulated to arise from DHA's pleiotropic effects on AD pathophysiology, including its effects on β-amyloid (Aβ) production, aggregation, and toxicity. While in vitro studies suggest that DHA may inhibit and reverse the formation of toxic Aβ oligomers, it remains uncertain whether these mechanisms operate in vivo at the physiological concentrations ...[more]

PMID: 26369878

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Dataset Information

Dietary DHA supplementation in an APP/PS1 transgenic rat model of AD reduces behavioral and A? pathology and modulates A? oligomerization.

Publications

Dietary DHA supplementation in an APP/PS1 transgenic rat model of AD reduces behavioral and Aβ pathology and modulates Aβ oligomerization.

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