%0 Journal Article %J J Alzheimers Dis %D 2021 %T High Fat Diet Mediates Amyloid-β Cleaving Enzyme 1 Phosphorylation and SUMOylation, Enhancing Cognitive Impairment in APP/PS1 Mice. %A Bao, Jian %A Liang, Zheng %A Gong, Xiaokang %A Yu, Jing %A Xiao, Yifan %A Liu, Wei %A Wang, Xiaochuan %A Wang, Jian-Zhi %A Shu, Xiji %X

BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia in older adults and extracellular accumulation of amyloid-β (Aβ) is one of the two characterized pathologies of AD. Obesity is significantly associated with AD developing factors. Several studies have reported that high fat diet (HFD) influenced Aβ accumulation and cognitive performance during AD pathology. However, the underlying neurobiological mechanisms have not yet been elucidated.

OBJECTIVE: The objective of this study was to explore the underlying neurobiological mechanisms of HFD influenced Aβ accumulation and cognitive performance during AD pathology.

METHODS: 2.5-month-old male APP/PS1 mice were randomly separated into two groups: 1) the normal diet (ND) group, fed a standard diet (10 kcal%fat); and 2) the HFD group, fed a high fat diet (40 kcal%fat, D12492; Research Diets). After 4 months of HFD or ND feeding, mice in the two groups were subjected for further ethological, morphological, and biochemical analyses.

RESULTS: A long-term HFD diet significantly increased perirenal fat and impaired dendritic integrity and aggravated neurodegeneration, and augmented learning and memory deficits in APP/PS1 mice. Furthermore, the HFD increased beta amyloid cleaving enzyme 1 (BACE1) dephosphorylation and SUMOylation, resulting in enhanced enzyme activity and stability, which exacerbated the deposition of amyloid plaques.

CONCLUSION: Our study demonstrates that long-term HFD consumption aggravates amyloid-β accumulation and cognitive impairments, and that modifiable lifestyle factors, such as obesity, can induce BACE1 post-modifications which may contribute to AD pathogenesis.

%B J Alzheimers Dis %V 85 %P 863-876 %8 2022 Jan 18 %G eng %N 2 %R 10.3233/JAD-215299 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Moringa Oleifera Alleviates Homocysteine-Induced Alzheimer's Disease-Like Pathology and Cognitive Impairments. %A Mahaman, Yacoubou Abdoul Razak %A Huang, Fang %A Wu, Mengjuan %A Wang, Yuman %A Wei, Zhen %A Bao, Jian %A Salissou, Maibouge Tanko Mahamane %A Ke, Dan %A Wang, Qun %A Liu, Rong %A Wang, Jian-Zhi %A Zhang, Bin %A Chen, Dan %A Wang, Xiaochuan %X

Alzheimer's disease (AD) is multifactorial with unclear etiopathology. Due to the complexity of AD, many attempted single therapy treatments, like Aβ immunization, have generally failed. Therefore, there is a need for drugs with multiple benefits. Naturally occurring phytochemicals with neuroprotective, anti-amyloidogenic, antioxidative, and anti-inflammatory properties could be a possible way out. In this study, the effect of Moringa oleifera (MO), a naturally occurring plant with high antioxidative, anti-inflammatory, and neuroprotective effects, was evaluated on hyperhomocysteinemia (HHcy) induced AD-like pathology in rats. Homocysteine (Hcy) injection for 14 days was used to induce AD-like pathology. Simultaneous MO extract gavage followed the injection as a preventive treatment or, after injection completion, MO gavage was performed for another 14 days as a curative treatment. MO was found to not only prevent but also rescue the oxidative stress and cognitive impairments induced by Hcy treatment. Moreover, MO recovered the decreased synaptic proteins PSD93, PSD95, Synapsin 1 and Synaptophysin, and improved neurodegeneration. Interestingly, MO decreased the Hyc-induced tau hyperphosphorylation at different sites including S-199, T-231, S-396, and S-404, and at the same time decreased Aβ production through downregulation of BACE1. These effects in HHcy rats were accompanied by a decrease in calpain activity under MO treatment, supporting that calpain activation might be involved in AD pathogenesis in HHcy rats. Taken together, our data, for the first time, provided evidence that MO alleviates tau hyperphosphorylation and Aβ pathology in a HHcy AD rat model. This and previous other studies support MO as a good candidate for, and could provide new insights into, the treatment of AD and other tauopathies.

%B J Alzheimers Dis %V 63 %P 1141-1159 %8 2018 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/29710724?dopt=Abstract %R 10.3233/JAD-180091