%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 2016 %T Altered Brain Activities Associated with Neural Repetition Effects in Mild Cognitive Impairment Patients. %A Yu, Jing %A Li, Rui %A Jiang, Yang %A Broster, Lucas S %A Li, Juan %X

Older adults with mild cognitive impairment (MCI) manifest impaired explicit memory. However, studies on implicit memory such as repetition effects in persons with MCI have been limited. In the present study, 17 MCI patients and 16 healthy normal controls (NC) completed a modified delayed-match-to-sample task while undergoing functional magnetic resonance imaging. We aim to examine the neural basis of repetition; specifically, to elucidate whether and how repetition-related brain responses are altered in participants with MCI. When repeatedly rejecting distracters, both NC and MCI showed similar behavioral repetition effects; however, in both whole-brain and region-of-interest analyses of functional data, persons with MCI showed reduced repetition-driven suppression in the middle occipital and middle frontal gyrus. Further, individual difference analysis found that activation in the left middle occipital gyrus was positively correlated with rejecting reaction time and negatively correlated with accuracy rate, suggesting a predictor of repetition behavioral performance. These findings provide new evidence to support the view that neural mechanisms of repetition effect are altered in MCI who manifests compensatory repetition-related brain activities along with their neuropathology.

%B J Alzheimers Dis %V 53 %P 693-704 %8 2016 May 11 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/27176074?dopt=Abstract %R 10.3233/JAD-160086