Article
Medicine, Research & Experimental
Zengtao Wang, Nidhi Sharda, Geoffry L. Curran, Ling Li, Val J. Lowe, Karunya K. Kandimalla
Summary: This study utilized dynamic imaging and pharmacokinetic modeling to investigate the accumulation kinetics of A beta peptides in the blood-brain barrier (BBB) endothelium. The results show that A beta 42 accumulates at a lower rate than A beta 40, and model simulations suggest that impaired exocytosis of A beta 42 leads to increased accumulation within the BBB endothelium.
MOLECULAR PHARMACEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Anna P. Tolstova, Alexei A. Adzhubei, Vladimir A. Mitkevich, Irina Yu Petrushanko, Alexander A. Makarov
Summary: This study identified the key interaction interfaces between RAGE and A beta isoforms and determined the chemical compounds that can potentially block this interaction. Molecular dynamics simulations showed that all A beta isoforms form stable and tightly bound complexes. These findings contribute to the understanding of the pathogenesis of Alzheimer's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Geriatrics & Gerontology
Qing-Qing Tao, Rong-Rong Lin, Yi-He Chen, Zhi-Ying Wu
Summary: Alzheimer's disease is the most common neurodegenerative disease characterized by the accumulation of Aβ and tau in the brain. The dysfunction of the blood brain barrier (BBB) is increasingly recognized as a causative factor of cognitive impairment, but its role in the pathogenesis of AD is still not fully understood. Additional research is needed to determine the underlying mechanisms between BBB dysfunction and AD, as well as explore new therapies for BBB regulation to treat AD in the future.
Article
Clinical Neurology
Bruna Bellaver, Albert Puig-Pijoan, Joao Pedro Ferrari-Souza, Douglas T. Leffa, Firoza Z. Lussier, Pamela C. L. Ferreira, Cecile Tissot, Guilherme Povala, Joseph Therriault, Andrea L. Benedet, Nicholas J. Ashton, Stijn Servaes, Mira Chamoun, Jenna Stevenson, Nesrine Rahmouni, Marie Vermeiren, Arthur C. Macedo, Aida Fernandez-Lebrero, Greta Garcia-Escobar, Irene Navalpotro-Gomez, Oscar Lopez, Dana L. Tudorascu, Ann Cohen, Victor L. Villemagne, William E. Klunk, Serge Gauthier, Eduardo R. Zimmer, Thomas K. Karikari, Kaj Blennow, Henrik Zetterberg, Marc Suarez-Calvet, Pedro Rosa-Neto, Tharick A. Pascoal
Summary: The permeability of the blood-brain barrier (BBB) may affect the levels of brain-derived proteins in the blood, which in turn can impact the relationship between brain and blood biomarkers. The study found that BBB permeability influenced the relationship between plasma A beta(42/40) and CSF A beta(42/40) as well as A beta-PET positivity, but did not significantly impact the relationship between brain and plasma p-tau levels.
ALZHEIMERS & DEMENTIA
(2023)
Article
Cell Biology
Tong Wu, Lizhi Chen, Lingqi Zhou, Jie Xu, Kaihua Guo
Summary: Platelets may play an important role in the pathogenesis of Alzheimer's disease, as their Aβ content increases with age and aged platelets can accelerate Aβ deposition in the brain, leading to learning and memory deficits in recipient mice. Administering aspirin as a platelet activation inhibitor effectively alleviated these toxic processes. In vitro blood-brain barrier models were used to explore the possible cytotoxicity of these platelets.
Article
Biochemistry & Molecular Biology
Sofia Toniolo, Francesco Di Lorenzo, Sergio Bernardini, Nicola Biagio Mercuri, Giulia Maria Sancesario
Summary: The definition of Alzheimer's disease (AD) now includes the presence of amyloid (A), tau deposition (T), and neurodegeneration (N) markers as essential for diagnosis. The relationship between blood-brain barrier (BBB) dysfunction and AD-specific biomarkers needs attention as blood-based biomarkers are being used more frequently. Factors such as age, gender, and ApoE status have previously been linked to BBB permeability. In this study, BBB dysfunction was not different across ATN subtypes and was not correlated with cognitive impairment, but patients with BBB disruption had low levels of A beta 40, and ApoE status affected the A beta 42/40 ratio.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Yurii A. Zolotarev, Vladimir A. Mitkevich, Stanislav I. Shram, Alexei A. Adzhubei, Anna P. Tolstova, Oleg B. Talibov, Alexander K. Dadayan, Nikolai F. Myasoyedov, Alexander A. Makarov, Sergey A. Kozin
Summary: The study showed that HAEE can cross the blood-brain barrier and interact directly with A beta, reducing cerebral amyloidogenesis in a mouse model of AD. This anti-amyloid effect is likely due to the interaction between HAEE and A beta species in the brain.
Article
Biotechnology & Applied Microbiology
Ruiyi Zhou, Lihong Zhu, Zhaohao Zeng, Rixin Luo, Jiawei Zhang, Rui Guo, Lei Zhang, Qunying Zhang, Wei Bi
Summary: In this study, a brain-targeted nanomedicine was designed for the treatment of Alzheimer's disease. The results showed that the nanomedicine had favorable biocompatibility and could effectively reduce amyloid deposition, improve neuronal damage, and enhance learning and memory capability.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Bibiana C. Mota, Nathan Ashburner, Laura Abelleira-Hervas, Liyueyue Liu, Robertas Aleksynas, Lucio Claudio Rovati, Gianfranco Caselli, Magdalena Sastre
Summary: Recent evidence suggests that I2-imidazoline ligands have neuroprotective properties in animal models of neurodegeneration, such as Alzheimer's disease (AD). In this study, the therapeutic potential of the powerful analgesic I2-imidazoline ligand CR4056 in the 5xFAD model of AD was evaluated. The results showed that CR4056 improved recognition memory, suppressed pro-inflammatory microglia, and restored fibrinogen extravasation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Yan-Li Zhang, Juan Wang, Zhi-Na Zhang, Qiang Su, Jun-Hong Guo
Summary: Neurovascular dysfunction plays an important role in the development and progression of chronic neurodegenerative processes in Alzheimer's disease. The blood-brain barrier (BBB) pathway is crucial for the clearance of amyloid-beta (A beta) in the brain, and endothelial cells are key players in A beta transport. Dysregulation of A beta clearance is considered the main reason for its accumulation in the brain. Understanding the interactions between A beta and brain capillary endothelial cells, including their receptors and transporters, may provide new therapeutic strategies for A beta clearance in Alzheimer's disease.
NEURAL REGENERATION RESEARCH
(2022)
Review
Cell Biology
Yan-Li Zhang, Juan Wang, Zhi-Na Zhang, Qiang Su, Jun-Hong Guo
Summary: Neurovascular dysfunction plays an important role in the onset and progression of Alzheimer's disease, and the blood-brain barrier pathway is a key pathway for amyloid-beta (Aβ) clearance in the brain. Brain capillary endothelial cells are crucial for Aβ clearance mediated by the blood-brain barrier. Dysregulation of Aβ clearance leads to its accumulation in the brain parenchyma. Understanding the interactions between Aβ and brain capillary endothelial cells and developing new therapeutic strategies could improve Aβ clearance in Alzheimer's disease.
NEURAL REGENERATION RESEARCH
(2022)
Article
Neurosciences
Kassandra Kisler, Abhay P. Sagare, Divna Lazic, Sam Bazzi, Erica Lawson, Ching-Ju Hsu, Yaoming Wang, Anita Ramanathan, Amy R. Nelson, Zhen Zhao, Berislav V. Zlokovic
Summary: PICALM is a significant susceptibility factor for Alzheimer's disease and plays a role in Aβ clearance at the blood-brain barrier. The anti-malaria drug artesunate can increase PICALM levels, reduce Aβ deposition, and improve cerebral blood flow and behavior in mice. This research is important for the treatment of Alzheimer's disease.
MOLECULAR NEURODEGENERATION
(2023)
Article
Clinical Neurology
Tobias Gustavsson, Nicole G. Metzendorf, Elin Wik, Sahar Roshanbin, Ulrika Julku, Aikaterini Chourlia, Per Nilsson, Ken G. Andersson, Hanna Laudon, Greta Hultqvist, Stina Syvanen, Dag Sehlin
Summary: In this study, the therapeutic efficacy of A beta targeting antibody RmAb158 and its bispecific variant RmAb158-scFv8D3 was compared. Both antibodies achieved positive effects in long-term treatment, but the bispecific antibody's limited plasma exposure may hinder its application in chronic therapy as a result of interactions with TfR or the immune system.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Article
Materials Science, Multidisciplinary
Shiting Song, Jingwen Wu, Ying Cheng, Lixiang Ma, Tao Liu, Jia Liu, Jun Liu, Jaroslaw Sotor, Ping Luan
Summary: Two-dimensional nanomaterials have shown potential in pharmaceutical applications, especially in the diagnosis and treatment of Alzheimer's disease (AD). They can improve the accuracy and specificity of AD biomarkers detection and inhibit A beta aggregation in treatment. However, resolving in vivo cytotoxicity remains a challenge.
APPLIED MATERIALS TODAY
(2021)
Article
Clinical Neurology
Andrew G. Murchison
Summary: This article posits that amyloid deposition and increased permeability of the blood-brain barrier are early independent events in Alzheimer's disease pathophysiology, contributing to a distinct microglial activation phenotype. Downstream effects such as synapse phagocytosis and persistent glutamate signally through NMDA receptors lead to neurodegeneration and tau pathology. This hypothesis aims to shed light on unexplained temporal and spatial features of AD by drawing from multiple lines of evidence.
ALZHEIMERS & DEMENTIA
(2022)
Article
Chemistry, Medicinal
Parul Goel, Thorsten Jumpertz, Anezka Ticha, Isabella Ogorek, David C. Mikles, Martin Hubalek, Claus U. Pietrzik, Kvido Strisovsky, Boris Schmidt, Sascha Weggen
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2018)
Article
Psychiatry
Sylvie L. Lesuis, Sascha Weggen, Sandra Baches, Paul J. Lucassen, Harm J. Krugers
TRANSLATIONAL PSYCHIATRY
(2018)
Article
Clinical Neurology
Susanne Walter, Thorsten Jumpertz, Melanie Huettenrauch, Isabella Ogorek, Hermeto Gerber, Steffen E. Storck, Silvia Zampar, Mitko Dimitrov, Sandra Lehmann, Klaudia Lepka, Carsten Berndt, Jens Wiltfang, Christoph Becker-Pauly, Dirk Beher, Claus U. Pietrzik, Patrick C. Fraering, Oliver Wirths, Sascha Weggen
ACTA NEUROPATHOLOGICA
(2019)
Article
Clinical Neurology
Stefan Reuss, Elena Siebrecht, Ulla Stier, Hans-Georg Buchholz, Nicole Bausbacher, Nadine Schabbach, Andrea Kronfeld, Marianne Dieterich, Mathias Schreckenberger
FRONTIERS IN NEUROLOGY
(2020)
Article
Radiology, Nuclear Medicine & Medical Imaging
Florian Rosar, Hans-Georg Buchholz, Sebastian Michels, Manuela A. Hoffmann, Markus Piel, Christopher M. Waldmann, Frank Roesch, Stefan Reuss, Mathias Schreckenberger
Article
Clinical Neurology
Freyja Aichholzer, Hans-Wolfgang Klafki, Isabella Ogorek, Jonathan Vogelgsang, Jens Wiltfang, Norbert Scherbaum, Sascha Weggen, Oliver Wirths
Summary: Despite the correlation between CSF GPNMB levels and other parameters such as aging and CSF pTau levels, the study results indicate that GPNMB levels in CSF cannot distinguish between AD or other neurological diseases. The findings do not support GPNMB as a valuable neurochemical diagnostic biomarker of AD, suggesting the need for further studies involving healthy control individuals.
ALZHEIMERS RESEARCH & THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Martina Stazi, Sandra Lehmann, M. Sadman Sakib, Tonatiuh Pena-Centeno, Luca Buschgens, Andre Fischer, Sascha Weggen, Oliver Wirths
Summary: Research suggests that moderate caffeine consumption reduces the risk of Alzheimer's disease and can improve neuronal loss, behavioral deficits, and neurogenesis in mouse models of the disease. The study challenges the belief that caffeine is anti-amyloidogenic and highlights the potential role of promoting neurogenesis in its beneficial effects.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Liana Marengo, Fred Armbrust, Caroline Schoenherr, Steffen E. Storck, Ulrich Schmitt, Silvia Zampar, Oliver Wirths, Hermann Altmeppen, Markus Glatzel, Christoph Kaether, Sascha Weggen, Christoph Becker-Pauly, Claus U. Pietrzik
Summary: This study reports the generation of a transgenic mouse model of AD lacking the functional Mep1b gene (APP/lon x Mep1b(-/-)). The results showed that when meprin beta is absent, the levels of A beta 1-40 and 1-42 are reduced in APP/lon mice, and the deposition of N-terminally truncated A beta 2-x peptide is also decreased. Importantly, the loss of meprin beta improved cognitive abilities in APP/lon mice.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Alexander D. Mazura, Anke Ohler, Steffen E. Storck, Magdalena Kurtyka, Franka Scharfenberg, Sascha Weggen, Christoph Becker-Pauly, Claus U. Pietrzik
Summary: Despite the lack of available therapies for Alzheimer's disease, research has found that reducing circulating PCSK9 levels can improve the clearance of cerebral amyloid-beta and reduce the burden of disease-related pathology in the brain, as well as improve memory processing.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Philip H. H. Klecker, Laura Fritzen, Alexander D. D. Mazura, Sascha Weggen, Claus U. U. Pietrzik
Summary: The preferred therapy for acute ischemic stroke is the use of Alteplase, a drug containing the enzyme tPA which destabilizes blood clots. BBB breakdown, associated with TJ protein degradation, is a significant issue in stroke pathology and appears to be more severe during therapy. The exact mechanisms of how tPA causes BBB breakdown are not fully understood, but it is believed that interaction with LRP1 is necessary for this effect. This study found that tPA does not change the barrier properties of microvascular endothelial cells but does affect microglial activation and BBB breakdown.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2023)
Article
Biology
Angelika Sabine Bader, Marius-Uwe Gnaedig, Merle Fricke, Luca Bueschgens, Lena Josefine Berger, Hans-Wolfgang Klafki, Thomas Meyer, Olaf Jahn, Sascha Weggen, Oliver Wirths
Summary: Senile plaques consisting of amyloid-beta (A beta) peptides are a major pathological hallmark of Alzheimer's disease (AD). A beta 1-40 and A beta 1-42 are considered canonical full-length A beta species. In 5XFAD mice, overall plaque load increased in the subiculum, hippocampus, and cortex, with the subiculum having the highest plaque coverage. The load of A beta 1-x peaked at five months and decreased thereafter in the subiculum, while plaques positive for truncated A beta 4-x species increased continuously over time. We hypothesize ongoing plaque remodeling leads to conversion of A beta 1-x peptides into A beta 4-x peptides in brain regions with high A beta plaque burden.
Article
Biochemistry & Molecular Biology
Stefan Reuss, Denise Linsmayer, Julia Balmaceda-Braun, Julia von Rittberg, Stephanie Mitz, Ursula Disque-Kaiser, Ted Usdin, Rudolf E. Leube
Summary: The distribution of synaptoporin in the central auditory system of mouse brainstem was investigated. Region-specific differences in synaptoporin immunostaining were observed, with high accumulation in certain areas known to be associated with extra-auditory inputs. Synaptoporin-positive synapses were found to be associated with certain types of neurons, but not with others. Furthermore, it was determined that synaptoporin-positive neurons do not originate in the medial paralemniscal nucleus, but their close proximity to other markers suggests coordinated action of different inputs.
JOURNAL OF CHEMICAL NEUROANATOMY
(2023)
Editorial Material
Neurosciences
Stefan Reuss
JOURNAL OF INTEGRATIVE NEUROSCIENCE
(2023)
Article
Neurosciences
Stefan Reuss
Summary: Through research on Djungarian hamsters, the location and distribution of spinal sympathetic preganglionic neurons projecting to the superior cervical ganglion have been identified. These neurons are mainly located in thoracic spinal segments and predominantly found in the intermediolateral nucleus of the spinal cord. The neurons produce nitric oxide and are associated with specific neurotransmitters.
JOURNAL OF INTEGRATIVE NEUROSCIENCE
(2021)
Article
Medicine, Research & Experimental
Anfei Huang, Prashant Shinde, Jun Huang, Tina Senff, Haifeng C. Xu, Cassandra Margotta, Dieter Hussinger, Thomas E. Willnow, Jinping Zhang, Aleksandra A. Pandyra, Jorg Timm, Sascha Weggen, Karl S. Lang, Philipp A. Lang
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)
