Review
Biochemistry & Molecular Biology
Junpei Takeishi, Yasuko Tatewaki, Taizen Nakase, Yumi Takano, Naoki Tomita, Shuzo Yamamoto, Tatsushi Mutoh, Yasuyuki Taki
Summary: Recent studies have shown a strong association between type 2 diabetes mellitus and Alzheimer's disease, partly due to insulin resistance and declining insulin signaling and receptor numbers in the brain. Glucose hypometabolism is observed in the brain of AD patients before symptoms appear, suggesting that promoting ketone metabolism could be a reasonable pathway for neuronal protection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Yanchao Liu, Shujuan Zhang, Benrong He, Liangkai Chen, Dan Ke, Shi Zhao, Yao Zhang, Wei Wei, Zhipeng Xu, Zihui Xu, Ying Yin, Wen Mo, Yanni Li, Yang Gao, Shihong Li, Weijin Wang, Huiling Yu, Dongqin Wu, Guilin Pi, Tao Jiang, Mingmin Deng, Rui Xiong, Huiyang Lei, Na Tian, Ting He, Fei Sun, Qiuzhi Zhou, Xin Wang, Jinwang Ye, Mengzhu Li, Nan Hu, Guoda Song, Wenju Peng, Chenghong Zheng, Huaqiu Zhang, Jian-Zhi Wang
Summary: Elevation of plasma A beta 1-42/A beta 1-40 is an independent risk factor of MCI in T2DM patients. Combining elevated A beta 1-42/A beta 1-40 with activated platelet GSK-3 beta, ApoE epsilon 4 genotype, olfactory decline, and aging increases the efficiency of MCI diagnosis in T2DM patients.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Qi Wang, Hong Li, Henghao Lu, Shumin Wang, Yuxiu Li, Zhenfen Zhang, Jing Han, Zhe Yang, Yanping Yang, Yan Hong
Summary: This study investigates the role of SAA1 in promoting T2DM and pancreatic beta-cell dysfunction. The findings indicate that SAA1 inhibits insulin secretion and promotes apoptosis in beta-cells, and this effect can be reduced by NF-kappa B signaling inhibitors.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Ryusuke Takechi, Arazu Sharif, Emily Brook, Maimuna Majimbi, Dick C. Chan, Virginie Lam, Gerald F. Watts, John C. L. Mamo
Summary: There is increasing evidence suggesting a positive association between type 2 diabetes and Alzheimer's disease (AD), mainly due to vascular dysfunction, insulin resistance, and accumulation of amyloid-beta protein (A beta) in the brain. Recent studies have found that A beta is secreted in the periphery as nascent triglyceride-rich lipoproteins (TRL's). Elevated levels of TRL-A beta in the blood compromise the blood-brain barrier (BBB), leading to neuroinflammation and cognitive decline. Inhibition of TRL-A beta secretion by peripheral lipogenic organs attenuates the AD phenotype, indicating a causal relationship. Poorly controlled type 2 diabetes often exhibits high triglyceride levels, which contribute to the development of Alzheimer's through increased lipoprotein-A beta and BBB breakdown. This review emphasizes the microvascular axis for dementia in diabetes and discusses potential pharmacotherapies to target insulin resistance, dyslipidemia, and plasma amyloidosis in type 2 diabetes.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Neurosciences
Yifan Xiao, Xiaokang Gong, Ronghua Deng, Wei Liu, Youhua Yang, Xiaochuan Wang, Jianzhi Wang, Jian Bao, Xiji Shu
Summary: The study found that a high-fat diet led to nonheme iron overload in the brains of AD mice, but iron chelation treatment could alleviate memory deficits caused by HFD and effectively reduce synaptic impairment in the hippocampus and neuronal degeneration in the cortex.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Geriatrics & Gerontology
Wen Zhang, Jiaming Lu, Zhao Qing, Xin Zhang, Hui Zhao, Yan Bi, Bing Zhang
Summary: This study found that subcortical structural alterations are related to cognitive decline in patients with type 2 diabetes. However, the impact of type 2 diabetes on Alzheimer's pathology remains unclear.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Review
Endocrinology & Metabolism
Thomas A. A. Lutz
Summary: Although small rodents are the most widely used animal models to study diabetes mellitus, non-rodent species like pigs, cats, and dogs also provide valuable insights. Animal models, including both rodents and non-rodent species, are essential for studying energy balance, metabolism control, and the development of metabolic diseases like type 2 diabetes mellitus. This Review outlines the advantages and disadvantages of selected animal models and aims to establish a basis for their appropriate use in biomedical research.
NATURE REVIEWS ENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Giuseppe Della Pepa, Valentina Brancato, Giuseppina Costabile, Dominic Salamone, Alessandra Corrado, Marilena Vitale, Carlo Cavaliere, Marcello Mancini, Marco Salvatore, Delia Luongo, Gabriele Riccardi, Angela A. Rivellese, Giovanni Annuzzi, Lutgarda Bozzetto
Summary: An isocaloric multifactorial diet including beneficial dietary components can significantly reduce pancreatic fat and improve postprandial insulin response in patients with type 2 diabetes.
Review
Biochemistry & Molecular Biology
Michalis Michailidis, Despina Moraitou, Despina A. Tata, Kallirhoe Kalinderi, Theodora Papamitsou, Vasileios Papaliagkas
Summary: This review article discusses the shared pathophysiological connections between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM), emphasizing the role of insulin in the brain and the mechanistic interplay between the two diseases. The findings highlight the need for routine evaluation and treatment of cognitive impairment in T2DM patients and the evaluation of insulin levels or T2DM in AD patients. The hypothesis of AD as a type 3 diabetes is strongly supported.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
John T. Walker, Diane C. Saunders, Vivek Rai, Hung-Hsin Chen, Peter Orchard, Chunhua Dai, Yasminye D. Pettway, Alexander L. Hopkirk, Conrad V. Reihsmann, Yicheng Tao, Simin Fan, Shristi Shrestha, Arushi Varshney, Lauren E. Petty, Jordan J. Wright, Christa Ventresca, Samir Agarwala, Radhika Aramandla, Greg Poffenberger, Regina Jenkins, Shaojun Mei, Nathaniel J. Hart, Sharon Phillips, Hakmook Kang, Dale L. Greiner, Leonard D. Shultz, Rita Bottino, Jie Liu, Jennifer E. Below, Stephen C. J. Parker, Alvin C. Powers, Marcela Brissova
Summary: Integration of multiomics data with functional analysis of pancreatic tissues from individuals with early-stage type 2 diabetes indicates that the genetic risk converges on RFX6, which regulates chromatin architecture at multiple risk loci.
Review
Engineering, Chemical
Yanxian Zhang, Yijing Tang, Dong Zhang, Yonglan Liu, Jian He, Yung Chang, Jie Zheng
Summary: The research focuses on the mechanism of amyloid cross-seeding between Aβ and hIAPP and its connection between AD and T2D, explores the role of structural compatibility and sequence similarity of amyloid proteins in cross-seeding, and proposes current challenges and future research directions in this less-studied field.
CHINESE JOURNAL OF CHEMICAL ENGINEERING
(2021)
Article
Nutrition & Dietetics
Yue Zhao, Qing-Yu Wang, Lv-Tao Zeng, Jing-Jing Wang, Zhen Liu, Guo-Qing Fan, Jin Li, Jian-Ping Cai
Summary: Long-term consumption of a high-fat, high-fructose diet can lead to pancreatic islet functional decay, which may be a potential mechanism of type 2 diabetes mellitus. This study reveals the structural and transcriptomic changes that occur in the pancreas under the influence of HFHF diet and aging.
Article
Medicine, Research & Experimental
Roy Taylor, Alison C. Barnes, Kieren G. Hollingsworth, Keaton M. Irvine, Alexandra S. Solovyova, Lucy Clark, Tara Kelly, Carmen Martin-Ruiz, Davide Romeres, Albert Koulman, Claire M. Meek, Benjamin Jenkins, Claudio Cobelli, Rury R. Holman
Summary: Weight loss in overweight or obese individuals with Type 2 diabetes can normalize hepatic fat metabolism, improve insulin secretion, and control blood glucose levels. The Personal Fat Threshold hypothesis suggests that different individuals have varying thresholds for the adverse effects of excess fat on beta-cell function. Through weight loss, beta-cell function and blood glucose levels can be restored, leading to sustained diabetes remission.
Article
Endocrinology & Metabolism
Hajime Yamazaki, Shinichi Tauchi, Juergen Machann, Tobias Haueise, Yosuke Yamamoto, Mitsuru Dohke, Nagisa Hanawa, Yoshihisa Kodama, Akio Katanuma, Norbert Stefan, Andreas Fritsche, Andreas L. Birkenfeld, Robert Wagner, Martin Heni
Summary: This study found that different patterns of fat distribution are associated with the risk of type 2 diabetes, with hepatic steatosis, pancreatic steatosis, and trunk myosteatosis being associated with higher risk.
Article
Endocrinology & Metabolism
Laila Silamikele, Ivars Silamikelis, Monta Ustinova, Zane Kalnina, Ilze Elbere, Ramona Petrovska, Ineta Kalnina, Janis Klovins
Summary: The study aimed to investigate the effect of metformin on gut microbiome in a high-fat diet-induced type 2 diabetes mouse model, utilizing shotgun metagenomic sequencing for the first time in mice study. The results showed significant alterations in gut microbiome diversity, composition, and functional implications, with sex-specific differences observed in response to metformin treatment. These findings suggest the importance of including both sexes in future studies focusing on metformin effects on gut microbiome.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Letter
Clinical Neurology
Takafumi Wada, Atsushi Shima, Akira Kuzuya, Takakuni Maki, Hirofumi Yamashita, Ryosuke Takahashi
ACTA NEUROLOGICA BELGICA
(2023)
Article
Clinical Neurology
Kaori Miwa, Masatoshi Koga, Manabu Inoue, Sohei Yoshimura, Makoto Sasaki, Yusuke Yakushiji, Mayumi Fukuda-Doi, Yasushi Okada, Taizen Nakase, Masafumi Ihara, Yoshinari Nagakane, Shunya Takizawa, Koko Asakura, Junya Aoki, Kazumi Kimura, Haruko Yamamoto, Kazunori Toyoda
Summary: New cerebral microbleeds developed within 36 h in 11% of patients after intravenous thrombolysis, and they were significantly associated with mixed-distribution and >= 5 cerebral microbleeds.
INTERNATIONAL JOURNAL OF STROKE
(2022)
Review
Clinical Neurology
Kazunori Toyoda, Sohei Yoshimura, Mayumi Fukuda-Doi, Adnan Qureshi, Renee' Hebert Martin, Yuko Y. Palesch, Masafumi Ihara, Jose Suarez, Yasushi Okada, Chung Y. Hsu, Ryo Itabashi, Yongjun Wang, Hiroshi Yamagami, Thorsten Steiner, Nobuyuki Sakai, Byung-Woo Yoon, Manabu Inoue, Kazuo Minematsu, Haruko Yamamoto, Masatoshi Koga
Summary: The study showed that rapid lowering of systolic blood pressure by continuous administration of intravenous nicardipine in patients with hyperacute intracerebral hemorrhage was associated with lower risks of hematoma expansion and 90-day death or disability, without increasing serious adverse events.
INTERNATIONAL JOURNAL OF STROKE
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
Masafumi Ihara
CIRCULATION RESEARCH
(2022)
News Item
Clinical Neurology
Masafumi Ihara, Yumi Yamamoto
Summary: Single-cell transcriptomic analyses of human brain microvessels have identified transcriptomic signatures and transcriptional changes in the cerebrovasculature in neurodegenerative diseases, which could significantly contribute to our understanding of brain health and disease.
NATURE REVIEWS NEUROLOGY
(2022)
Article
Clinical Neurology
Junpei Koge, Kanta Tanaka, Takeshi Yoshimoto, Masayuki Shiozawa, Yuji Kushi, Tsuyoshi Ohta, Tetsu Satow, Hiroharu Kataoka, Masafumi Ihara, Masatoshi Koga, Noriko Isobe, Kazunori Toyoda
Summary: Tortuosity of the internal carotid artery (ICA) affects the outcomes of mechanical thrombectomy, with lower first pass effect rate and higher risk of intracranial hemorrhage in patients with greater tortuosity.
Article
Clinical Neurology
Kanta Tanaka, Masatoshi Koga, Mayumi Fukuda-Doi, Adnan Qureshi, Haruko Yamamoto, Kaori Miwa, Masafumi Ihara, Kazunori Toyoda
Summary: This study used group-based trajectory modeling to analyze blood pressure changes in patients with acute intracerebral hemorrhage receiving antihypertensive treatment, and found that different blood pressure trajectories were associated with different outcomes. Specifically, the high-to-low SBP group showed increased risks of death or disability and acute kidney injury.
Review
Clinical Neurology
Yumi Yamamoto, Yi-Chu Liao, Yi-Chung Lee, Masafumi Ihara, Jay Chol Choi
Summary: CADASIL is the most common monogenic disorder of the cerebral small blood vessels, caused by mutations in the NOTCH3 gene. Recent large-scale genomic studies have revealed a high prevalence of pathogenic NOTCH3 variants among the general population, with the highest risk being among Asians. The exact pathogenesis of CADASIL remains unclear, despite various laboratory and clinical observations being made.
JOURNAL OF CLINICAL NEUROLOGY
(2023)
Article
Nutrition & Dietetics
Takayuki Inoue, Bin Fu, Miwako Nishio, Miyako Tanaka, Hisashi Kato, Masashi Tanaka, Michiko Itoh, Hajime Yamakage, Kozue Ochi, Ayaka Ito, Yukihiro Shiraki, Satoshi Saito, Masafumi Ihara, Hideo Nishimura, Atsuhiko Kawamoto, Shian Inoue, Kumiko Saeki, Atsushi Enomoto, Takayoshi Suganami, Noriko Satoh-Asahara
Summary: The molecular pathogenesis of nonalcoholic steatohepatitis (NASH) involves metabolic stress and inflammatory stimuli. In this study, we found that Taxifolin treatment effectively prevented hepatic steatosis, chronic inflammation, and liver fibrosis in a NASH murine model. Taxifolin inhibited lipid accumulation in hepatocytes and increased brown adipose tissue activity. Furthermore, Taxifolin treatment after NASH development could prevent the development of liver tumors. These findings indicate the pleiotropic effects of Taxifolin for NASH treatment.
Editorial Material
Biochemistry & Molecular Biology
Hiroyuki Ishiyama, Masafumi Ihara
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Nutrition & Dietetics
Masayo Iwasa, Hisashi Kato, Kaori Iwashita, Hajime Yamakage, Sayaka Kato, Satoshi Saito, Masafumi Ihara, Hideo Nishimura, Atsuhiko Kawamoto, Takayoshi Suganami, Masashi Tanaka, Noriko Satoh-Asahara
Summary: This study found that a high-glucose environment can increase intracellular reactive oxygen species (ROS) levels and trigger inflammation in microglial cells, leading to cognitive impairment in diabetes. However, taxifolin, a natural flavonoid, has been shown to reduce ROS levels and inhibit the activation of the TXNIP-NLRP3 axis, thereby suppressing inflammation and preventing cognitive impairment in diabetes.
Letter
Clinical Neurology
Yoshito Arakaki, Takeshi Yoshimoto, Hiroyuki Ishiyama, Tomotaka Tanaka, Yorito Hattori, Masafumi Ihara
JOURNAL OF MOVEMENT DISORDERS
(2023)
Article
Health Care Sciences & Services
Satoshi Suda, Takehiro Katano, Kazuo Kitagawa, Yasuyuki Iguchi, Shigeru Fujimoto, Kenjiro Ono, Osamu Kano, Hidehiro Takekawa, Masatoshi Koga, Masafumi Ihara, Masafumi Morimoto, Hiroshi Yamagami, Tadashi Terasaki, Keiji Yamaguchi, Seiji Okubo, Yuji Ueno, Nobuyuki Ohara, Yuki Kamiya, Masataka Takeuchi, Yukako Yazawa, Yuka Terasawa, Ryosuke Doijiri, Yoshifumi Tsuboi, Kazutaka Sonoda, Koichi Nomura, Takashi Shimoyama, Akihito Kutsuna, Kazumi Kimura
Summary: This study aims to evaluate the proportion, timing, and characteristics of atrial fibrillation (AF) detection in patients with cryptogenic stroke (CS) using insertable cardiac monitors (ICMs). It also aims to compare patient characteristics and outcomes between those with AF and those without AF. The study has started and the main results are expected to be published in 2023. The findings of this study will contribute to the identification of AF markers and the development of a new and improved screening algorithm for AF detection, as well as aiding in the selection of patients for ICM implantation and the development of diagnostic criteria for CS in Japan.
JMIR RESEARCH PROTOCOLS
(2023)
Article
Clinical Neurology
Takehito Kuroda, Tomotaka Tanaka, Soichiro Abe, Manabu Inoue, Yoshiaki Morita, Takuto Mukaida, Takamasa Iwai, Masafumi Ihara
EPILEPTIC DISORDERS
(2023)
Article
Medicine, General & Internal
Satoshi Suda, Chikako Nito, Masafumi Ihara, Yasuyuki Iguchi, Takao Urabe, Yuji Matsumaru, Nobuyuki Sakai, Kazumi Kimura
Summary: This study aims to evaluate the safety and efficacy of a novel cell-based therapy product called JTR-161 for patients with acute ischemic stroke. The study will be conducted in Japan and will use a randomized, double-blind, placebo-controlled design. The results of the study will be disseminated through informed consent forms and peer-reviewed publication.
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)