Correlations Between Single Nucleotide Polymorphisms, Cognitive Dysfunction, and Postmortem Brain Pathology in Alzheimer’s Disease Among Han Chinese

Yang, Qian; Chen, Kang; Zhang, Hanlin; Zhang, Wanying; Gong, Changlin; Zhang, Qing; Liu, Pan; Sun, Tianyi; Xu, Yuanyuan; Qian, Xiaoxian; Qiu, Wenying; Ma, Chao

doi:10.1007/s12264-019-00343-2

Cited by 9 publications

(5 citation statements)

References 59 publications

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“…Recently, several rare mutations have been associated with late-onset AD (LOAD) in the prodomain of ADAM10, and two mutations promote amyloid pathology by diminishing α-secretase activity 40 . This year, a genome-wide association study (GWAS) identified a common variant in ADAM10 which was associated with increased AD risk 41 , which has been confirmed in Han Chinese population 42 . These findings suggest that decreased levels and activity of ADAM10 are involved in AD pathogenesis, and ADAM10 is a promising therapeutic target 43 .…”

Section: Discussionmentioning

confidence: 94%

Capsaicin consumption reduces brain amyloid-beta generation and attenuates Alzheimer’s disease-type pathology and cognitive deficits in APP/PS1 mice

et al. 2020

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Alzheimer's disease (AD) is the most common cause of age-related dementia and is currently incurable. The failures of current clinical trials and the establishment of modifiable risk factors have shifted the AD intervention from treatment to prevention in the at-risk population. Previous studies suggest that there is a geographic overlap between AD incidence and spicy food consumption. We previously reported that capsaicin-rich diet consumption was associated with better cognition and lower serum Amyloid-beta (Aβ) levels in people aged 40 years and over. In the present study, we found that intake of capsaicin, the pungent ingredient in chili peppers, reduced brain Aβ burden and rescued cognitive decline in APP/PS1 mice. Our in vivo and in vitro studies revealed that capsaicin shifted Amyloid precursor protein (APP) processing towards α-cleavage and precluded Aβ generation by promoting the maturation of a disintegrin and metalloproteinase 10 (ADAM10). We also found that capsaicin alleviated other AD-type pathologies, such as tau hyperphosphorylation, neuroinflammation and neurodegeneration. The present study suggests that capsaicin is a potential therapeutic candidate for AD and warrants clinical trials on chili peppers or capsaicin as dietary supplementation for the prevention and treatment of AD.

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Section: Discussionmentioning

confidence: 94%

Capsaicin consumption reduces brain amyloid-beta generation and attenuates Alzheimer’s disease-type pathology and cognitive deficits in APP/PS1 mice

et al. 2020

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“…Genetic factors most likely determine the rate of disease progression (e.g., the brain-derived neurotrophic factor polymorphism) [ 19 , 20 ]. In Han Chinese, a study showed that APOE-e4, the RS2305421 GG genotype, and the RS10498633 GT genotype are associated with the Aβ plaque score, Braak neurofibrillary tangle stage, and CERAD (Consortium to Establish a Registry for Alzheimer's disease) neuritic plaque score; these results have advanced our understanding of the pathogenesis of AD [ 21 ].…”

Section: Pathogeneses and Pathological Changes In Admentioning

confidence: 99%

Comprehensive Management of Daily Living Activities, behavioral and Psychological Symptoms, and Cognitive Function in Patients with Alzheimer's Disease: A Chinese Consensus on the Comprehensive Management of Alzheimer's Disease

Jia

Liu

et al. 2021

Neurosci. Bull.

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Alzheimer's disease (AD) is the most common cognitive disorder in the elderly. Its main clinical manifestations are cognitive decline (C), behavioral and psychological symptoms (B), and a decline in the activities of daily living (A), also known as ABC symptoms. Early identification and evaluation of ABC symptoms are helpful for establishing the accurate diagnosis, comprehensive treatment, and prognosis of AD. To guide Chinese clinical practice for optimization of the comprehensive management of AD, in 2018, The Academy of Cognitive Disorder of China gathered 22 neurologists and gerontologists in China to build a consensus on the comprehensive management of AD. Based on a review of the evidence, the consensus summarizes the pathogenesis, pathological changes, clinical manifestations, evaluation, diagnosis, drug and non-drug treatment, and patient care for AD. Focus group discussion was used to establish a flowchart of comprehensive ABC management for AD patients. The new consensus provides a feasible AD management process for clinicians.

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“…Dense-core Aβ plaques are one of the major components of AD neuropathology [ 72 ]. Importantly, the number of dense-core plaques is positively correlated with the severity of AD neuropathological changes and cognitive decline [ 73 , 74 ]. The positive correlation between the density of dense-core plaques and Braak stage in AD found in our study demonstrates that advanced dementia corresponds with high levels of AD neuropathological changes.…”

Section: Discussionmentioning

confidence: 99%

Increased cysteinyl-tRNA synthetase drives neuroinflammation in Alzheimer’s disease

Qi,

Chen,

Wang

et al. 2024

Transl Neurodegener

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Background Microglia-mediated neuroinflammation in Alzheimer’s disease (AD) is not only a response to pathophysiological events, but also plays a causative role in neurodegeneration. Cytoplasmic cysteinyl-tRNA synthetase (CARS) is considered to be a stimulant for immune responses to diseases; however, it remains unknown whether CARS is involved in the pathogenesis of AD. Methods Postmortem human temporal cortical tissues at different Braak stages and AD patient-derived serum samples were used to investigate the changes of CARS levels in AD by immunocytochemical staining, real-time PCR, western blotting and ELISA. After that, C57BL/6J and APP/PS1 transgenic mice and BV-2 cell line were used to explore the role of CARS protein in memory and neuroinflammation, as well as the underlying mechanisms. Finally, the associations of morphological features among CARS protein, microglia and dense-core plaques were examined by immunocytochemical staining. Results A positive correlation was found between aging and the intensity of CARS immunoreactivity in the temporal cortex. Both protein and mRNA levels of CARS were increased in the temporal cortex of AD patients. Immunocytochemical staining revealed increased CARS immunoreactivity in neurons of the temporal cortex in AD patients. Moreover, overexpression of CARS in hippocampal neurons induced and aggravated cognitive dysfunction in C57BL/6J and APP/PS1 mice, respectively, accompanied by activation of microglia and the TLR2/MyD88 signaling pathway as well as upregulation of proinflammatory cytokines. In vitro experiments showed that CARS treatment facilitated the production of proinflammatory cytokines and the activation of the TLR2/MyD88 signaling pathway of BV-2 cells. The accumulation of CARS protein occurred within dense-core Aβ plaques accompanied by recruitment of ameboid microglia. Significant upregulation of TLR2/MyD88 proteins was also observed in the temporal cortex of AD. Conclusions The findings suggest that the neuronal CARS drives neuroinflammation and induces memory deficits, which might be involved in the pathogenesis of AD.

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Correlations Between Single Nucleotide Polymorphisms, Cognitive Dysfunction, and Postmortem Brain Pathology in Alzheimer’s Disease Among Han Chinese

Cited by 9 publications

References 59 publications

Capsaicin consumption reduces brain amyloid-beta generation and attenuates Alzheimer’s disease-type pathology and cognitive deficits in APP/PS1 mice

Capsaicin consumption reduces brain amyloid-beta generation and attenuates Alzheimer’s disease-type pathology and cognitive deficits in APP/PS1 mice

Comprehensive Management of Daily Living Activities, behavioral and Psychological Symptoms, and Cognitive Function in Patients with Alzheimer's Disease: A Chinese Consensus on the Comprehensive Management of Alzheimer's Disease

Increased cysteinyl-tRNA synthetase drives neuroinflammation in Alzheimer’s disease

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