Review
Neurosciences
Octavio Garcia, Lisi Flores-Aguilar
Summary: Down syndrome is caused by the triplication of human chromosome 21, leading to intellectual disability. Individuals with DS may develop clinical symptoms associated with Alzheimer's disease in middle adulthood.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Review
Immunology
Deepali Singh
Summary: Neuroinflammation is caused by the misfiring of immune cells in the central nervous system and can have both positive and negative effects on neurodevelopment and post-injury tissue. Chronic or uncontrolled inflammatory responses may lead to neurodegenerative diseases, while abnormal activation of glial cells can mediate neuroinflammation.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Clinical Neurology
Amy M. Smith, Karen Davey, Stergios Tsartsalis, Combiz Khozoie, Nurun Fancy, See Swee Tang, Eirini Liaptsi, Maria Weinert, Aisling McGarry, Robert C. J. Muirhead, Steve Gentleman, David R. Owen, Paul M. Matthews
Summary: The study reveals significant differences in gene expression in astrocytes and microglia in the brains of AD patients, correlated with amyloid-beta or pTau expression. There are distinct gene expression patterns in the two cell types and pathologies, but common gene sets exist in each cell type. Additionally, different sub-clusters are found in astrocytes and microglia, characterized by transcriptional signatures related to either homeostatic functions or disease pathology.
ACTA NEUROPATHOLOGICA
(2022)
Review
Biochemistry & Molecular Biology
Aditya Sunkaria, Supriya Bhardwaj
Summary: Poor quality and quantity of sleep are common in elderly people worldwide, and sleep disturbances may accelerate neurodegeneration. Glial cells are implicated in the progression of Alzheimer's disease and play a role in regulating sleep homeostasis.
NEUROCHEMICAL RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Yuanxin Zhao, Buhan Liu, Jian Wang, Long Xu, Sihang Yu, Jiaying Fu, Xiaoyu Yan, Jing Su
Summary: Neuroinflammation mediated by microglia is a common feature in neurodegenerative diseases. The accumulation of Aβ and tau proteins can disrupt the metabolism of microglia, leading to neuroinflammation.
Article
Multidisciplinary Sciences
Hannah Ennerfelt, Coco Holliday, Daniel A. Shapiro, Kristine E. Zengeler, Ashley C. Bolte, Tyler K. Ulland, John R. Lukens
Summary: Recent advances have shown the importance of microglia-expressed innate immune receptors in Alzheimer's disease (AD), specifically TREM2, CD33, and CD22. However, the downstream signaling molecules used by these receptors in AD are still not well understood. This study demonstrates that CARD9, an intracellular adaptor molecule, plays a crucial role in A(3-mediated disease and microglial responses in AD.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Alice Filippini, Valentina Salvi, Vincenzo Dattilo, Chiara Magri, Stefania Castrezzati, Robert Veerhuis, Daniela Bosisio, Massimo Gennarelli, Isabella Russo
Summary: The accumulation of amyloid-beta in Alzheimer's disease (AD) brains causes reactive astrogliosis and neuroinflammatory response. This study investigates the role of leucine-rich repeat kinase 2 (LRRK2) in regulating astrocytic activation in response to amyloid-beta(1-42) (A beta(1-42)). The results demonstrate that LRRK2 kinase activity modulates astrocytic reactivity and functions in the presence of A beta(1-42) deposits, suggesting a potential contribution of PD-linked LRRK2 to AD-related neuroinflammation and pathogenesis.
Article
Clinical Neurology
Nicola Spotorno, Olof Strandberg, Geraline Vis, Erik Stomrud, Markus Nilsson, Oskar Hansson
Summary: Metrics of cortical microstructural alteration derived from diffusion MRI are highly sensitive to multiple aspects of the Alzheimer's disease pathological cascade, particularly the associations with Aβ-PET and GFAP, making them important outcome measures in clinical trials for disease-modifying therapies.
Article
Neurosciences
Luciana Domett Siqueira, Ana Paula M. Celes, Hellin Dos Santos, Sergio T. Ferreira
Summary: The study showed that the AZ formulation had protective effects against glial cell activation and memory deficits induced by A beta Os in a mouse model of AD, suggesting a promising preventative and non-pharmacological strategy to reduce brain inflammation and attenuate memory impairment in AD.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Neurosciences
Printha Wijesinghe, Clayton A. Whitmore, Matthew Campbell, Charles Li, Miranda Tsuyuki, Eleanor To, Justin Haynes, Wellington Pham, Joanne A. Matsubara
Summary: The naturally occurring dietary antioxidant Ergothioneine (Ergo) can promote the clearance of amyloid beta (Aβ), possibly by enhancing blood-derived phagocytic macrophages and perivascular drainage. This finding provides a clue for further investigation of the mechanisms underlying the role of Ergo in Alzheimer's disease.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Clinical Neurology
Rebecca L. Winfree, Mabel Seto, Logan Dumitrescu, Vilas Menon, Philip De Jager, Yanling Wang, Julie Schneider, David A. Bennett, Angela L. Jefferson, Timothy J. Hohman
Summary: This study investigated the correlation between region-specific TREM2 mRNA expression and neuropathology measures in a large sample size. The results showed that TREM2 expression was related to Alzheimer's disease pathology, cerebrovascular pathology, microglial activation, and cognitive decline, but the associations varied across different brain regions. These findings suggest that TREM2's pathological associations are dependent on the brain region.
ACTA NEUROPATHOLOGICA
(2023)
Article
Neurosciences
Mary Elizabeth Curtis, Tiffany Smith, Miroslav Nenov, Benjamin E. Blass, Domenico Pratico
Summary: Pharmacological stabilization of the retromer complex improves synaptic plasticity and memory in a mouse model of Down syndrome, supporting the therapeutic potential of pharmacological retromer stabilization for individuals with Down syndrome.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Plant Sciences
Min-Ji Jung, Namkwon Kim, Seung Ho Jeon, Min Sung Gee, Ji-Woon Kim, Jong Kil Lee
Summary: The study investigated the effects of eugenol on Alzheimer's disease (AD) and found that eugenol effectively improved cognitive function and reduced pathological changes in 5xFAD mice. The underlying mechanisms may involve inhibiting neuronal cell death and promoting beta-amyloid clearance.
Article
Neurosciences
Thomas J. LaRocca, Alyssa N. Cavalier, Christine M. Roberts, Maddie R. Lemieux, Pooja Ramesh, Micklaus A. Garcia, Christopher D. Link
Summary: The amyloid beta (A beta) peptide is believed to have a central role in Alzheimer's disease by synergistically promoting pro-inflammatory activation in primary human astrocytes with known cytokines. By directly substituting for the complement component C1q in a cytokine cocktail, A beta activates astrocytes similarly to neurotoxic astrocytes found in brain aging and AD. The biological action of A beta at low concentrations is distinct from that of high doses typically used in in vitro studies.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Cell Biology
Savannah Tallino, Wendy Winslow, Samantha K. Bartholomew, Ramon Velazquez
Summary: This study investigated the accumulation of soluble Aβ(40-42) in the Ts65Dn mouse model, revealing age-specific differences and sex disparities in different brain regions. The results indicated that trisomic mice started accumulating Aβ(40-42) in the frontal cortex and hippocampus as early as 4 months of age, with females showing significantly higher levels of Aβ(40-42) in the basal forebrain at 7-8 months old. Additionally, the study found an inverse correlation between APP expression and Aβ(40-42) levels in the basal forebrain and hippocampus.
Article
Biochemical Research Methods
Tomer Illouz, Ravit Madar, Eitan Okun
JOURNAL OF NEUROSCIENCE METHODS
(2020)
Article
Neurosciences
Moshe Hagar, Gersner Roman, Okun Eitan, Barnea-Ygael Noam, Zangen Abrham, Sredni Benjamin
NEUROMOLECULAR MEDICINE
(2020)
Editorial Material
Geriatrics & Gerontology
Raneen Nicola, Eitan Okun
FRONTIERS IN AGING NEUROSCIENCE
(2020)
Article
Biochemistry & Molecular Biology
Liroy Lugasi, Igor Grinberg, Rivka Sabag, Ravit Madar, Haim Einat, Shlomo Margel
Review
Neurosciences
Tavor Ben-Zeev, Eitan Okun
Summary: High-intensity interval training (HIIT) and strength exercise are beneficial for improving health markers such as cardiovascular health, metabolic health, and cognitive function, reducing all-cause mortality. High-Intensity Functional Training (HIFT) combines HIIT and strength exercise to enhance muscle recruitment, improving both cardiovascular fitness and strength parameters. This review focuses on the molecular mechanisms underlying the positive effects of HIFT on cardiovascular, metabolic, and cognitive functions.
NEUROMOLECULAR MEDICINE
(2021)
Article
Biology
Tomer Illouz, Raneen Nicola, Linoy Ben-Shushan, Ravit Madar, Arya Biragyn, Eitan Okun
Summary: A study by Illouz et al. demonstrated that maternal immunization with anti-A beta antibodies in wildtype female mice bred with 5xFAD males led to reduced cortical A beta levels and alleviated memory deficits in the offspring, even 4 months after the antibodies were undetectable. This long-term effect was attributed to a shift in microglial phenotype. The findings suggest that maternal immunization could potentially alleviate cognitive decline and pathology associated with early A beta deposition in diseases like AD and DS.
COMMUNICATIONS BIOLOGY
(2021)
Review
Neurosciences
Raneen Nicola, Eitan Okun
Summary: Adult hippocampal neurogenesis is a dynamic process involving cognitive functions such as learning and memory, regulated by numerous intrinsic and extrinsic factors. Physical exercise, particularly the impact of lactate, plays a beneficial role in neural plasticity. Lactate, considered a potent factor in health and disease, influences most cells in the CNS and affects different cell types within the neurogenic niche, regulating adult hippocampal neurogenesis.
NEUROMOLECULAR MEDICINE
(2021)
Article
Multidisciplinary Sciences
Ki Kim, Xin Wang, Emeline Ragonnaud, Monica Bodogai, Tomer Illouz, Marisa DeLuca, Ross A. McDevitt, Fedor Gusev, Eitan Okun, Evgeny Rogaev, Arya Biragyn
Summary: The study demonstrates that accumulation of activated B cells is crucial to the pathology of AD in three relevant transgenic animal models, and depletion of B cells interferes with both histological and behavioral manifestations of the disease.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Tomer Illouz, Ravit Madar, Tamir Hirsh, Arya Biragyn, Eitan Okun
Summary: The decline in immune functions related to aging, known as immunosenescence, leads to reduced protective responses to vaccines in the elderly. Developing vaccination strategies that harness memory-based immunity can overcome this age-related decline in immune responses and have potential implications for aging-related diseases such as Alzheimer's disease.
Article
Neurosciences
Raneen Nicola, Ravit Madar, Eitan Okun
Summary: A recent study found that extracellular lactate can reduce the phagocytic ability of microglial cells by binding to a specific receptor, potentially impacting brain homeostasis and inflammatory conditions.
NEUROMOLECULAR MEDICINE
(2022)
Letter
Immunology
Wan-Ju Cheng, Hong-Mo Shih, Kuan-Pin Su, Po-Ren Hsueh
BRAIN BEHAVIOR AND IMMUNITY
(2024)
Article
Immunology
Felipe Kenji Sudo, Talita P. Pinto, Fernanda G. Q. Barros-Aragao, Ivanei Bramati, Theo F. Marins, Marina Monteiro, Fernanda Meireles, Rejane Soares, Pilar Erthal, Victor Calil, Naima Assuncao, Natalia Oliveira, Joana Bondarovsky, Camila Lima, Beatriz Chagas, Alana Batista, Julia Lins, Thais L. Pinheiro, Felippe Mendonca, Andrea Silveira de Souza, Fernanda C. Rodrigues, Gabriel R. de Freitas, Pedro Kurtz, Paulo Mattos, Erika C. Rodrigues, Fernanda G. De Felice, Fernanda Tovar-Moll
Summary: Post-COVID-19 Condition (PCC) is a multisystemic syndrome that persists for months after SARS-CoV-2 infection, affecting cognitive function and neuropsychiatric features. A study on COVID-19 survivors in Brazil found that these patients experienced significant difficulties in overall cognition, memory, working memory, and inhibitory control, as well as fatigue, anxiety, and depressive symptoms. In addition, elevated levels of inflammatory markers in the blood were associated with brain microstructural damage and cognitive impairments.
BRAIN BEHAVIOR AND IMMUNITY
(2024)
Letter
Immunology
Tieh-Cheng Fu, Juei-Chao Chen, Ching-Mao Chang
BRAIN BEHAVIOR AND IMMUNITY
(2024)
Article
Immunology
Aastha Dheer, Dale B. Bosco, Jiaying Zheng, Lingxiao Wang, Shunyi Zhao, Koichiro Haruwaka, Min-Hee Yi, Abhijeet Barath, Dai-Shi Tian, Long-Jun Wu
Summary: Microglial activation plays a crucial role in the pathology of epilepsy, with both acute and prolonged activation affecting seizure severity and neuronal loss.
BRAIN BEHAVIOR AND IMMUNITY
(2024)
Article
Immunology
Julie B. Rosenberg, Jens Richardt Mollegaard Jepsen, Parisa Mohammadzadeh, Astrid Sevelsted, Rebecca Vinding, Mikkel E. Sorensen, David Horner, Kristina Aagaard, Birgitte Fagerlund, Susanne Brix, Nilofar Folsgaard, Ann -Marie M. Schoos, Jakob Stokholm, Bo Chawes, Christos Pantelis, Soren Dalsgaard, Birte Y. Glenthoj, Niels Bilenberg, Klaus Bonnelykke, Bjorn H. Ebdrup
Summary: Clinical data demonstrates a strong association between prenatal maternal inflammation assessed by hs-CRP and a diagnosis of ADHD by age 10. Maternal inflammation is also associated with ADHD symptom load in the entire cohort.
BRAIN BEHAVIOR AND IMMUNITY
(2024)
Article
Immunology
Suzanne M. Green-Fulgham, Michael J. Lacagnina, Kendal F. Willcox, Jiahe Li, Michael E. Harland, Adriano Polican Ciena, Igor R. Correia Rocha, Jayson B. Ball, Renee A. Dreher, Younus A. Zuberi, Joseph M. Dragavon, Marucia Chacur, Steven F. Maier, Linda R. Watkins, Peter M. Grace
Summary: Regular aerobic activity, specifically voluntary wheel running, can reduce the risk of chronic pain by inhibiting MAC and preserving myelin integrity at the site of peripheral nerve injury.
BRAIN BEHAVIOR AND IMMUNITY
(2024)
Article
Immunology
India Boyton, Stella M. Valenzuela, Lyndsey E. Collins-Praino, Andrew Care
Summary: Neuronanomedicine is a multidisciplinary field that aims to develop innovative nanotechnologies for the treatment of neurodegenerative disorders. Nanoparticles are an important component of neuronanomedicine, as they can improve drug properties and enhance safety and delivery across the blood-brain barrier. However, a major challenge for neuronanomedicine translation is the poor understanding of bio-nano interactions, partly due to inconsistent reporting in published works. This review provides specific recommendations to guide researchers in harnessing the unique properties of nanoparticles for breakthrough treatments of Alzheimer's and Parkinson's disease.
BRAIN BEHAVIOR AND IMMUNITY
(2024)
Article
Immunology
Celine De Looze, Cathal McCrory, Aisling O'Halloran, Silvia Polidoro, Rose Anne Kenny, Joanne Feeney
Summary: Our study found that subjective measures of stress and biological metrics may be independently associated with cognitive function over time in older adults, hinting at potential different underlying mechanisms.
BRAIN BEHAVIOR AND IMMUNITY
(2024)
Article
Immunology
Beatrice Bravi, Elisa Maria Teresa Melloni, Marco Paolini, Mariagrazia Palladini, Federico Calesella, Laura Servidio, Elena Agnoletto, Sara Poletti, Cristina Lorenzi, Cristina Colombo, Francesco Benedetti
Summary: Depressed patients show changes in immune-inflammatory markers in their blood and cerebrospinal fluid. The Choroid Plexus, located at the base of the brain ventricles, plays a key role in regulating the exchange of substances between the brain and immune cells. Patients with bipolar disorder or major depressive disorder have larger Choroid Plexus volumes compared to healthy controls. Age and levels of circulating cytokines are associated with Choroid Plexus volumes in the clinical groups.
BRAIN BEHAVIOR AND IMMUNITY
(2024)
Article
Immunology
Mingxuan Zheng, Huaiyu Ye, Xiaoying Yang, Lijun Shen, Xuemei Dang, Xiaoli Liu, Yuying Gong, Qingyuan Wu, Li Wang, Xing Ge, Xiaoli Fang, Benchi Hou, Peng Zhang, Renxian Tang, Kuiyang Zheng, Xu-Feng Huang, Yinghua Yu
Summary: Obesity is linked to cognitive dysfunction and neurodegenerative disease. The connection between the gut microbiota and the brain is altered in obesity. The probiotic Clostridium butyricum can improve cognitive impairment caused by obesity and prevent gut microbiota dysbiosis and inflammation.
BRAIN BEHAVIOR AND IMMUNITY
(2024)
Article
Immunology
Edward Drydale, Phalguni Rath, Katie Holden, Gregory Holt, Laurissa Havins, Thomas Johnson, James Bancroft, Lahiru Handunnetthi
Summary: This study created a novel three-dimensional neurosphere assay using induced pluripotent stem cell differentiation and live cell imaging techniques to investigate the effect of a simulated viral infection on cortical development. The findings demonstrated that the infection led to reduced radial glial growth and neural migration.
BRAIN BEHAVIOR AND IMMUNITY
(2024)
Article
Immunology
Yuancheng Weng, Ningting Chen, Rui Zhang, Jian He, Xukai Ding, Guo Cheng, Qianqian Bi, Ying-mei Lu, Xiao Z. Shen, Shu Wan, Peng Shi
Summary: This study reveals that microglia is the primary cellular source of PDGFB in adults, and microglial PDGFB is crucial for maintaining BBB integrity in adult mice.
BRAIN BEHAVIOR AND IMMUNITY
(2024)
Article
Immunology
Evan A. Bordt, Haley A. Moya, Young Chan Jo, Caitlin T. Ravichandran, Izabella M. Bankowski, Alexis M. Ceasrine, Christopher J. Mcdougle, William A. Carlezon Jr, Staci D. Bilbo
Summary: There is a strong male bias in many neurodevelopmental disorders such as autism spectrum disorder, but the mechanisms behind this bias are unknown. Infection during the perinatal period increases the risk of neurodevelopmental disorders. Using a mouse model, researchers found that early-life immune activation only induced deficits in social behaviors in male mice. These behavioral changes were associated with alterations in microglial immune signaling, mitochondrial morphology, gene expression, and function specifically in microglia, the brain's innate immune cells. Furthermore, the vulnerability to early-life immune activation and its effects on behavior and microglial mitochondria were programmed by the male-typical perinatal gonadal hormone surge. These findings highlight the role of microglia-specific mechanisms shaped by early developmental events in regulating male social behavior throughout lifespan.
BRAIN BEHAVIOR AND IMMUNITY
(2024)
Article
Immunology
Maria Amalia Di Castro, Stefano Garofalo, Alessandro Mormino, Laura Carbonari, Erika Di Pietro, Eleonora De Felice, Myriam Catalano, Laura Maggi, Cristina Limatola
Summary: Cytokines, such as interleukin-15 (IL-15), play important roles in modulating the central nervous system (CNS). In this study, the authors found that exposure to IL-15 enhances GABA release and reduces glutamatergic currents in hippocampal slices. Chronic treatment with IL-15 has negative effects on memory formation. Serotonin is involved in mediating these effects, as a selective 5-HT3A receptor antagonist prevents the effects on inhibitory neurotransmission and improves performance in a memory test.
BRAIN BEHAVIOR AND IMMUNITY
(2024)
Article
Immunology
Nikhitha Sreenivas, Michael Maes, Hansashree Padmanabha, Apoorva Dharmendra, Priyanka Chakkera, Saptamita Paul Choudhury, Fazal Abdul, Thrinath Mullapudi, Vykuntaraju K. Gowda, Michael Berk, John Vijay Sagar Kommu, Monojit Debnath
Summary: Neurodevelopmental disorders (NDDs) are a spectrum of conditions with both common and differing characteristics in terms of phenome, symptomatome, neuropathology, risk factors and underlying mechanisms. This study investigates the possibility of a shared immune etiology among three early-onset NDDs, namely Autism Spectrum Disorder (ASD), Attention Deficit Hyperactivity Disorder (ADHD) and Intellectual Disability Disorder (IDD).
BRAIN BEHAVIOR AND IMMUNITY
(2024)