Article
Pharmacology & Pharmacy
Rose Chesworth, David Cheng, Chloe Staub, Tim Karl
Summary: Cannabidiol (CBD) therapy shows potential in preventing cognitive impairment in female genetically modified mouse models of Alzheimer's disease (AD), suggesting a preventive therapeutic effect in female familial AD patients.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Neurosciences
Ana C. Sanchez-Hidalgo, Francisco Arias-Arag, M. Teresa Romero-Barrag, Celia Martin-Cuevas, Jose M. Delgado-Garcia, Amalia Martinez-Mir, Francisco G. Scholl
Summary: The study indicates that dysfunction in PS/gamma-secretase complex may lead to neuronal deficits in familial Alzheimer's disease. Transgenic mice models in the research show an association between the accumulation of NrxnCTF and impairments in associative memory and short-term synaptic plasticity.
EXPERIMENTAL NEUROLOGY
(2022)
Article
Neurosciences
Lihong Zhu, Qiongru Yuan, Zhaohao Zeng, Ruiyi Zhou, Rixin Luo, Jiawei Zhang, Chi Kwan Tsang, Wei Bi
Summary: The study demonstrates that rifampicin improves cognitive impairment induced by LPS by enhancing autophagy, inhibiting Aβ(1-42) accumulation, and enhancing neurological function in the hippocampus.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Review
Endocrinology & Metabolism
Jenny Szu, Andre Obenaus
Summary: Alzheimer's disease is a devastating neurological disorder characterized by memory and cognitive decline, with two main hypotheses proposed regarding its underlying mechanisms. The amyloid hypothesis suggests A beta accumulation as the basis of AD, while the vascular hypothesis links early vascular damage to increased A beta deposits in the brain. Studies have shown significant morphological changes in the cerebrovasculature associated with AD progression, highlighting the need for further research in this area.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Article
Neurosciences
Dandan Wang, Kai Xu, Mingxi Dang, Feng Sang, Kewei Chen, Zhanjun Zhang, Xin Li
Summary: Understanding the relationship between amyloid-beta accumulation and cognition is important for studying the pathology of Alzheimer's disease. This study examined the regional accumulation of amyloid-beta and its relationship with various cognitive functions. The results showed that amyloid-beta accumulation was mainly found in the frontoparietal cortex, calcarine fissure, and surrounding cortex and temporal pole regions. Support vector machine analysis indicated that episodic memory-related regions had better classification performance during the progression of Alzheimer's disease. Assessing regional changes in amyloid, particularly in the frontoparietal regions, can help in the early detection of cognitive decline related to amyloid.
Review
Biochemistry & Molecular Biology
Raquel Sanchez-Varo, Marina Mejias-Ortega, Juan Jose Fernandez-Valenzuela, Cristina Nunez-Diaz, Laura Caceres-Palomo, Laura Vegas-Gomez, Elisabeth Sanchez-Mejias, Laura Trujillo-Estrada, Juan Antonio Garcia-Leon, Ines Moreno-Gonzalez, Marisa Vizuete, Javier Vitorica, David Baglietto-Vargas, Antonia Gutierrez
Summary: This review provides an overview of the major pathological elements of Alzheimer's disease and discusses the insights provided by mouse models in understanding the underlying mechanisms. It highlights the pros and cons of current models and explores the potential benefits of combining transgenic mice with omics technologies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Haitao Li, Yu Li, Wenping Liang, Zheng Z. Wei, Xuanyu Li, Yuanruhua Tian, Shanshan Qiao, Yishu Yang, Liu Yang, Dongyue Wu, Wei Yin, Honglin Liu, Wei Zhang, Yongbo Zhang, Zhe Wang
Summary: A novel PSEN1 p.Tyr159Ser mutation associated with early-onset Alzheimer's disease (EOAD) was identified. The mutation caused a significant increase in the Aβ42/Aβ40 ratio and had a notable impact on PS1 maturation. Other mutations or SNPs in different genes may modify the effects of this mutation, and their identification could facilitate the discovery of AD-preventing mechanisms and methods.
MOLECULAR AND CELLULAR NEUROSCIENCE
(2022)
Article
Geriatrics & Gerontology
Xuemeng Miao, Qian Wu, Siyu Du, Ludan Xiang, Siyao Zhou, Junzhe Zhu, Zirun Chen, Hui Wang, Xuyi Pan, Yiren Fan, Lihan Zhang, Jingkang Qian, Yuxuan Xing, Yiyang Xie, Lixin Hu, Haiyun Xu, Wei Wang, Ying Wang, Zhihui Huang
Summary: Neuroinflammation is crucial in the development and progression of Alzheimer's disease (AD), and SARM1 is known to promote axonal degeneration and be involved in neuroinflammation. This study showed that SARM1 was reduced in hippocampal neurons of AD model mice. Conditional knockout of SARM1 in the central nervous system delayed cognitive decline, reduced A beta deposition and inflammatory infiltration, and inhibited neurodegeneration in AD model mice. Further investigation revealed the downregulation of the TNF-alpha pathway in the hippocampus of SARM1 knockout mice, which alleviated cognitive decline, A beta deposition, and inflammatory infiltration.
Article
Neurosciences
Yu-Ting Hu, Xin-Lu Chen, Ya-Nan Zhang, Hugo McGurran, Jochem Stormmesand, Nicole Breeuwsma, Arja Sluiter, Juan Zhao, Dick Swaab, Ai-Min Bao
Summary: Epidemiological studies have shown that women have a higher prevalence of Alzheimer's disease (AD) than men. This study aimed to investigate the role of estrogen and the transcription factor EGR1 in AD pathogenesis using the 3xTg-AD mouse model. The results showed sex differences in levels of Aβ in the hippocampus and suggested that local E2 may have protective effects on EGR1 and cholinergic functions in AD.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Biochemical Research Methods
Satoshi Muraoka, Mark P. Jedrychowski, Naotoshi Iwahara, Mohammad Abdullah, Kristen D. Onos, Kelly J. Keezer, Jianqiao Hu, Seiko Ikezu, Gareth R. Howell, Steven P. Gygi, Tsuneya Ikezu
Summary: This study utilized high-resolution proteomic analysis of EVs isolated from an AD animal model to determine their content composition and cellular origin. The findings suggest the involvement of the A beta-processing complex and neurodegenerative microglia in EV secretion, shedding light on the pathogenesis of AD.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Jee Hyun Yi, Eunbi Cho, Soowon Lee, Seungheon Lee, Kyoung Ja Kwon, Juyong Lee, Changyeol Lee, Chan Young Shin, Dong Hyun Kim, Sang Hee Shim
Summary: The study found that the flavonoid pectolinarin can inhibit the aggregation of A beta and break down pre-formed aggregates, reducing their neurotoxicity. Additionally, pectolinarin can alleviate the reduction in long-term potentiation (LTP) induced by A beta aggregates. Oral administration of pectolinarin can improve memory impairment and LTP deficits caused by A beta injection.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Clinical Neurology
Tobey J. Betthauser, Murat Bilgel, Rebecca L. Koscik, Bruno M. Jedynak, Yang An, Kristina A. Kellett, Abhay Moghekar, Erin M. Jonaitis, Charles K. Stone, Corinne D. Engelman, Sanjay Asthana, Bradley T. Christian, Dean F. Wong, Marilyn Albert, Susan M. Resnick, Sterling C. Johnson
Summary: Alzheimer's disease biomarkers are crucial for understanding disease progression and predicting symptoms. This study develops and evaluates methods for modeling amyloid accumulation and investigates factors influencing the timing of amyloid onset and impairment onset. The findings suggest that APOE genotype, rather than sex, is associated with amyloid onset age, and that higher APOEe4 dosage, being female, and older amyloid onset age shorten the time from amyloid onset to dementia.
Article
Multidisciplinary Sciences
David Baglietto-Vargas, Stefania Forner, Lena Cai, Alessandra C. Martini, Laura Trujillo-Estrada, Vivek Swarup, Marie Minh Thu Nguyen, Kelly Do Huynh, Dominic Javonillo, Kristine Minh Tran, Jimmy Phan, Shan Jiang, Eniko A. Kramar, Cristina Nunez-Diaz, Gabriela Balderrama-Gutierrez, Franklin Garcia, Jessica Childs, Carlos J. Rodriguez-Ortiz, Juan Antonio Garcia-Leon, Masashi Kitazawa, Mohammad Shahnawaz, Dina P. Matheos, Xinyi Ma, Celia Da Cunha, Ken C. Walls, Rahasson R. Ager, Claudio Soto, Antonia Gutierrez, Ines Moreno-Gonzalez, Ali Mortazavi, Andrea J. Tenner, Grant R. MacGregor, Marcelo Wood, Kim N. Green, Frank M. LaFerla
Summary: The researchers created a mouse model that expresses wildtype human A β, demonstrating effects on cognition, synaptic plasticity, brain changes, inflammation, PAS granules, and gene expression. Furthermore, excision of exon 14 through Cre-mediated methods reduced A β expression and rescued cognitive impairments.
NATURE COMMUNICATIONS
(2021)
Article
Medicine, Research & Experimental
Hao-Yu Zou, Lin Guo, Bei Zhang, Si Chen, Xin-Rong Wu, Xian-Dong Liu, Xin-Yu Xu, Bin-Yin Li, Shengdi Chen, Nan-Jie Xu, Suya Sun
Summary: This study identifies the miR-339-5p/Nnat pathway as a crucial factor in the development of familial AD, highlighting its potential as a diagnostic and therapeutic target for early pathogenesis.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Biochemical Research Methods
Soumya Kandi, Erika N. Cline, Brianna M. Rivera, Kirsten L. Viola, Jiuhe Zhu, Carlo Condello, Richard D. Leduc, William L. Klein, Neil L. Kelleher, Steven M. Patrie
Summary: This study focuses on the role of different proteoforms of A beta in Alzheimer's disease. The authors evaluated the flux of A beta proteoforms using quantitative top-down mass spectrometry in a mouse model. They found 25 different forms of A beta with differential solubility in addition to the major A beta 1-42 form. These proteoforms were categorized into three groups based on expression levels and solubility. The findings suggest that this workflow has potential for investigating the relationship between insoluble fibrils and soluble A beta, as well as the role of low-molecular-weight oligomers in neurotoxicity. It may also help validate the use of AD-relevant animal models.
JOURNAL OF PROTEOME RESEARCH
(2023)