Article
Neurosciences
Jacob Kumro, Ashutosh Tripathi, Yun Lei, Jeremy Sword, Patrick Callahan, Alvin Terry, Xin-Yun Lu, Sergei A. Kirov, Anilkumar Pillai, David T. Blake
Summary: In this study, the activation of the basal forebrain was found to have positive effects on Alzheimer's model mice, including the activation of neurotrophins and the reduction of Aβ(42) generation and accumulation.
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
Agriculture, Multidisciplinary
Jian Bao, Zheng Liang, Xiaokang Gong, Yanna Zhao, Mengjuan Wu, Wei Liu, Chenyu Tu, Xiaochuan Wang, Xiji Shu
Summary: This study found that Tangeretin (TAN) exhibits antidementia activity in APPswe/PSEN1dE9 transgenic mice, reducing cognitive impairment, synaptic impairments, and beta-amyloid accumulations. TAN also showed powerful inhibitory activity against beta-secretase, suggesting it as a potential drug for preventing Alzheimer's disease pathology.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Laura Schnoeder, Inge Tomic, Laura Schwindt, Dominic Helm, Mandy Rettel, Walter Schulz-Schaeffer, Elmar Krause, Jens Rettig, Klaus Fassbender, Yang Liu
Summary: Deficiency of p38 alpha-MAPK in neurons leads to increased retrograde transportation of BACE1 in axons, shifting it from axonal terminals to lysosomes in the cell body, which exacerbates amyloid deposition in the brain of Alzheimer's disease.
Article
Multidisciplinary Sciences
Jiaojiao Tian, Miao Ren, Peilin Zhao, Shukang Luo, Yingying Chen, Xiaofeng Xu, Tao Jiang, Qingtao Sun, Anan Li, Hui Gong, Xiangning Li, Qingming Luo
Summary: Through synaptic connections, the brain forms functional motifs and executes specific functions. Researchers successfully mapped the whole-brain distribution and architecture of long projections of specific neurons, and found that synaptic degeneration was inconsistent with the accumulation of amyloid-beta plaques but was preferred in memory-related circuits.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Medicine, Research & Experimental
Marika Marino, Lujia Zhou, Melvin Y. Rincon, Zsuzsanna Callaerts-Vegh, Jens Verhaert, Jerome Wahis, Eline Creemers, Lidia Yshii, Keimpe Wierda, Takashi Saito, Catherine Marneffe, Iryna Voytyuk, Yessica Wouters, Maarten Dewilde, Sandra Duque, Cecile Vincke, Yona Levites, Todd E. Golde, Takaomi C. Saido, Serge Muyldermans, Adrian Liston, Bart De Strooper, Matthew G. Holt
Summary: Single domain antibodies (VHHs) have potential therapeutic value for neurological disorders, but their use in the central nervous system is limited by the blood-brain barrier. This study proposes a gene transfer strategy using BBB-crossing AAV-based vectors to deliver VHH directly into the CNS. The results show that AAV-delivered VHH can effectively inhibit BACE1 and improve cognitive performance in an Alzheimer's disease mouse model, providing a novel therapeutic approach for neurodegenerative diseases.
EMBO MOLECULAR MEDICINE
(2022)
Article
Neurosciences
Annie Y. Yao, Patrick J. Halloran, Yingying Ge, Neeraj Singh, John Zhou, James Galske, Wanxia He, Riqiang Yan, Xiangyou Hu
Summary: Alzheimer's disease (AD) patients have an increased risk of seizures and sleep disorders. Deletion of Bace1 in neurons increases epileptiform activity, while Bace1 inhibition can reduce epileptic activity and improve sleep disorders.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Biotechnology & Applied Microbiology
Jhilik Dey, Akanksha Roberts, Subhasis Mahari, Sonu Gandhi, Prem Prakash Tripathi
Summary: This study reports a method for rapid detection of BACE1 antigen for Alzheimer's disease diagnosis. By conjugating reduced graphene oxide with BACE1 antibody and immobilizing it on an electrode, the antigen can be detected within a short period of time. The method shows fast, sensitive, specific, and stable performance, making it a potential approach for early diagnosis of Alzheimer's disease.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Xiaotong Yang, Wenqin Yang, Xue Xia, Ting Lei, Zhihang Yang, Wenfeng Jia, Yang Zhou, Guo Cheng, Huile Gao
Summary: Alzheimer's disease (AD) is a common neurodegenerative disease with no effective treatment. In this study, a multifunctional nanocarrier was developed to deliver beta-site precursor protein cleaving enzyme-1 (BACE1) siRNA and rapamycin into the brain via intranasal administration. The results showed that this nanocarrier significantly improved the cognitive ability of transgenic AD mice.
Editorial Material
Biochemistry & Molecular Biology
Guncha Bhasin, Kirsten N. Calvin-Dunn, James M. Hyman
Summary: All animals use two strategies for navigation, involving movement or landmark-based navigation. A recent study shows that compromised movement-based navigation contributes to disrupted grid cell coding in an early Alzheimer's disease mouse model.
Article
Cell Biology
De-Juan Yuan, Guang Yang, Wei Wu, Qi-Fa Li, De-en Xu, Michael Ntim, Chun-Yan Jiang, Ji-Chuan Liu, Yue Zhang, Ying-Zi Wang, Dan-Dan Zhu, Supratik Kundu, Ai-Ping Li, Zhi-Cheng Xiao, Quan-Hong Ma, Shao Li
Summary: The reduction of VGSC alpha-subunit Nav1.6 in the hippocampus of APP/PS1 transgenic mice can improve cognitive impairments, attenuate synaptic deficits, reduce amyloid plaques, and lower levels of soluble A beta. Interfering with Nav1.6 suppresses BACE1 transcription, reduces intracellular calcium overload, and alleviates synaptic loss, ultimately improving learning and memory disorders in APP/PS1 mice. This study offers a potential therapeutic strategy for countering hippocampal hyperexcitability and rescuing cognitive deficits in AD by selectively targeting Nav1.6 overexpression and hyperactivity.
Article
Multidisciplinary Sciences
Benjamin L. Walker, Qing Nie
Summary: NeST is a method that extracts spatial gene expression structure through coexpression hotspots, which can identify structure on any spatial scale and any subset of genes, and are highly explainable. Furthermore, NeST performs spatial analysis of cell-cell interactions via ligand-receptor, identifying active areas without restriction of cell type or other groupings.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Kazuya Kobayashi, Takuya Otani, Saki Ijiri, Yuki Kawasaki, Hiroki Matsubara, Takahiro Miyagi, Taishi Kitajima, Risa Iseki, Katsuyasu Ishizawa, Naoka Shindo, Kouta Okawa, Kouta Ueda, Syun Ando, Momoka Kawakita, Yasunao Hattori, Kenichi Akaji
Summary: The introduction of an aromatic substituent into a HEA-type BACE1 inhibitor enhanced inhibitory activity, with the R-configuration improving activity and methyl substitution decreasing activity. Isosteres with different hydroxyl and methyl configurations were prepared using a branched synthesis approach, and the effect on inhibitory activity was evaluated. Derivatives with various substituents at the P1' site showed clear effects on BACE1 activity, leading to the identification of a highly potent inhibitor.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Neurosciences
Alexandra Badea, Didong Li, Andrei R. R. Niculescu, Robert J. J. Anderson, Jacques A. A. Stout, Christina L. L. Williams, Carol A. A. Colton, Nobuyo Maeda, David B. B. Dunson
Summary: Spatial navigation and orientation are promising markers for early cognitive changes in Alzheimer's disease, and different APOE gene alleles are associated with varying degrees of risk. A new metric, the absolute winding number, accurately assesses differences in spatial search strategies. This research provides insights into the mechanisms and diagnostic methods for Alzheimer's disease, and highlights the role of brain circuits and sex differences in spatial memory and navigation strategies.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Cell Biology
Shihong Li, Qiuzhi Zhou, Enjie Liu, Huiyun Du, Nana Yu, Haitao Yu, Weijin Wang, Mengzhu Li, Ying Weng, Yang Gao, Guilin Pi, Xin Wang, Dan Ke, Jian-Zhi Wang
Summary: The pathological accumulation of tau protein in mossy cells may induce spatial memory deficits resembling AD by inhibiting local neural network activity, revealing new pathogenesis and providing a mouse model for drug development.
Article
Geriatrics & Gerontology
Sarah N. Kraeutner, Cristina Rubino, Jennifer K. Ferris, Shie Rinat, Lauren Penko, Larissa Chiu, Brian Greeley, Christina B. Jones, Beverley C. Larssen, Lara A. Boyd
Summary: This study examined the age-related changes in brain function and baseline brain structure that support motor skill acquisition. The findings showed that older adults experienced decreases in functional connectivity during motor skill acquisition, while younger adults experienced increases. Additionally, regardless of age group, lower baseline microstructure in a frontoparietal tract was associated with slower motor skill acquisition.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Karen Nuytemans, Farid Rajabli, Melissa Jean-Francois, Jiji Thulaseedhara Kurup, Larry D. Adams, Takiyah D. Starks, Patrice L. Whitehead, Brian W. Kunkle, Allison Caban-Holt, Jonathan L. Haines, Michael L. Cuccaro, Jeffery M. Vance, Goldie S. Byrd, Gary W. Beecham, Christiane Reitz, Margaret A. Pericak-Vance
Summary: This study conducted genetic research on African American AD families and identified a significant linkage signal associated with AD, highlighting the importance of diverse population-level genetic data in understanding the genetic determinants of AD.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Kazuya Suwabe, Ryuta Kuwamizu, Kazuki Hyodo, Toru Yoshikawa, Takeshi Otsuki, Asako Zempo-Miyaki, Michael A. Yassa, Hideaki Soya
Summary: Physical exercise has a positive impact on hippocampal memory decline with aging. Recent studies have shown that even light exercise can improve memory and this improvement is mediated by the ascending arousal system. This study aimed to investigate the effects of light-intensity exercise on hippocampal memory function in healthy older adults and found that pupil dilation during exercise played a role in the memory improvement.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Ajay Sood, Ana Werneck Capuano, Robert Smith Wilson, Lisa Laverne Barnes, Alifiya Kapasi, David Alan Bennett, Zoe Arvanitakis
Summary: The objective of this study was to explore the impact of metformin on cognition and brain pathology. The results showed that metformin users had slower decline in global cognition, episodic memory, and semantic memory compared to non-users. However, the relationship between metformin use and certain brain pathology remains uncertain.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Brian N. Lee, Junwen Wang, Molly A. Hall, Dokyoon Kim, Shana D. Stites, Li Shen
Summary: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory and functional impairments. This study analyzed participants from the Alzheimer's Disease Neuroimaging Initiative and found differential associations between cerebral spinal fluid (CSF)/neuroimaging biomarkers and cognitive/functional outcomes, as well as variations between sexes. These findings suggest that sex differences may play a role in the development of AD.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Madeline R. Hale, Rebecca Langhough, Lianlian Du, Bruce P. Hermann, Carol A. Van Hulle, Margherita Carboni, Gwendlyn Kollmorgenj, Kristin E. Basche, Davide Bruno, Leah Sanson-Miles, Erin M. Jonaitis, Nathaniel A. Chin, Ozioma C. Okonkwo, Barbara B. Bendlin, Cynthia M. Carlsson, Henrik Zetterberg, Kaj Blennow, Tobey J. Betthauser, Sterling C. Johnson, Kimberly D. Mueller
Summary: This study demonstrates a relationship between cerebrospinal fluid biomarkers and the ability to recall proper names in the preclinical phase of Alzheimer's disease.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Thomas T. Austin, Christian L. Thomas, Ben Warren
Summary: This study investigated the effects of age on the robustness and resilience of auditory system using the desert locust. The researchers found that gene expression changes were mainly influenced by age rather than noise exposure. Both young and aged locusts were able to recover their auditory nerve function within 48 hours of noise exposure, but the recovery of transduction current magnitude was impaired in aged locusts. Key genes responsible for robustness to noise exposure in young locusts and potential candidates for compensatory mechanisms in auditory neurons of aged locusts were identified.
NEUROBIOLOGY OF AGING
(2024)