Article
Cell Biology
Sonia Do Carmo, Benjamin Kannel, A. Claudio Cuello
Summary: This article discusses the causes of the loss of basal forebrain cholinergic neurons in Alzheimer's disease (AD) and the role of nerve growth factor (NGF) in maintaining the cholinergic phenotype. Initially, a trophic failure of NGF was suspected, but it was found that NGF synthesis and abundance are normal in AD patients. The authors propose that trophic factor failure explains the atrophy of these neurons and discuss the dysregulation of NGF metabolism in AD pathology, suggesting its potential use in preclinical diagnosis.
Article
Biochemistry & Molecular Biology
Chiara Orciani, Helene Hall, Rowan Pentz, Morgan K. Foret, Sonia Do Carmo, Augusto Claudio Cuello
Summary: The destruction of cholinergic nuclei in the basal forebrain can impair cognition and reduce cortical neuron markers, while also affecting brain-derived neurotrophic factor (BDNF) levels, but not nerve growth factor (NGF) levels.
JOURNAL OF NEUROCHEMISTRY
(2022)
Review
Clinical Neurology
Ezio Giacobini, A. Claudio Cuello, Abraham Fisher
Summary: The review discusses the use of cholinesterase inhibitors in the treatment of Alzheimer's disease, the role of the basal forebrain cholinergic system in cognition, and potential future therapies targeting the NGF metabolic pathway and M1 muscarinic receptor. It provides an updated view of the cholinergic-oriented therapy of Alzheimer's disease and suggests new alternatives to enhance its clinical effect.
Article
Neurosciences
Selena Gonzalez, Tyne L. M. McHugh, Tao Yang, Wassim Syriani, Stephen M. Massa, Frank M. Longo, Danielle A. Simmons
Summary: The study identified a new drug, PTX-BD10-2, that can help restore symptomatic neuron degeneration in an Alzheimer's disease mouse model and has neuroprotective effects on neurons derived from human induced pluripotent stem cells.
NEUROBIOLOGY OF DISEASE
(2022)
Review
Geriatrics & Gerontology
Jose L. L. Martinez, Matthew D. D. Zammit, Nicole R. R. West, Bradley T. T. Christian, Anita Bhattacharyya
Summary: Down syndrome and Alzheimer's disease are both linked to cognitive impairment, with basal forebrain cholinergic neurons being vulnerable in both disorders, leading to memory loss and language disturbance. There are gaps in understanding the vulnerability of these neurons, limiting our ability to design effective interventions for individuals with DS and AD.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Neurosciences
Gaq Tu, Adel Halawa, Xiaotian Yu, Samuel Gillman, Kaori Takehara-Nishiuchi
Summary: Acetylcholine controls arousal, attention, and learning through regulating cortical excitability and plasticity. Recent research found that cholinergic neurons emit precise signals about aversive outcomes. This study manipulated cholinergic terminals in the mPFC and discovered that phasic cholinergic signaling plays a crucial role in aversive associative learning.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Ping Zhong, Qing Cao, Zhen Yan
Summary: Alzheimer's disease is a neurodegenerative disorder associated with cognitive decline. The study reveals that there are functional changes in the neural circuits between the prefrontal cortex and basal forebrain in a tauopathy mouse model, which may contribute to the loss of attention and executive function.
Article
Clinical Neurology
Mikahela A. Lopez-Morales, Iris Escobar, Isabel Saul, Charles W. Jackson, Fernando J. Ferrier, Eric A. Fagerli, Ami P. Raval, Kunjan R. Dave, Miguel A. Perez-Pinzon
Summary: This study reveals that focal cerebral ischemia leads to the death of cholinergic neurons in memory-relevant nuclei of the basal forebrain, and resveratrol preconditioning can prevent this cell loss, improve memory performance, and preserve the functionality of memory-processing brain structures.
Article
Biology
Blaise Robert, Eyal Y. Kimchi, Yurika Watanabe, Tatenda Chakoma, Miao Jing, Yulong Li, Daniel B. Polley
Summary: Research shows that basal forebrain cholinergic neurons have different functional characteristics in different regions, broadcasting diverse modulatory signals to downstream brain regions.
Article
Medicine, Research & Experimental
Yong-Xia Xu, Can Wang, Xiao-Die Li, Wen-Lu Guo, Guo-Ying Liu, Hua-Bing Zhang, Yan Sun, De-Fa Zhu, Qi Xu
Summary: Cognitive dysfunction is common in hypothyroid patients, even after sufficient levothyroxine replacement therapy. Cholinergic neurons play a role in this cognitive impairment. Activating the BF cholinergic neurons improves cognitive function through the BF-PFC and BF-hippocampus pathways.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biology
Maria Luisa Franco, Irmina Garcia-Carpio, Raquel Comaposada-Baro, Juan J. Escribano-Saiz, Lucia Chavez-Gutierrez, Marcal Vilar
Summary: Research shows that treatment with gamma-secretase inhibitors leads to the oligomerization of p75CTF, resulting in cell death of BFCNs, possibly mediated by TrkA activity. The findings suggest that inhibiting gamma-secretase activity in older patients may accelerate cholinergic dysfunction and neurodegeneration.
LIFE SCIENCE ALLIANCE
(2021)
Review
Neurosciences
Mala R. Ananth, Prithviraj Rajebhosale, Ronald Kim, David A. Talmage, Lorna W. Role
Summary: Acetylcholine plays a crucial role in cognition. Recent studies have revealed the complex organization and function of cholinergic neurons in the basal forebrain, and their involvement in diverse cognitive behaviors. These findings highlight the importance of cholinergic signaling in cognition.
NATURE REVIEWS NEUROSCIENCE
(2023)
Article
Behavioral Sciences
Anne S. Berry, Theresa M. Harrison
Summary: The basal forebrain cholinergic system (BFCS) has been associated with age-related cognitive changes and Alzheimer's disease (AD). Despite limitations in cholinergic interventions, there is a renewed interest in studying the BFCS using novel frameworks. This article outlines the structure and function of the BFCS, its role in cognition and emotion, and its vulnerability to aging and AD. It also explores the BFCS in relation to the amyloid hypothesis, selective vulnerability, pathology spread, and sleep health in AD research.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2023)
Review
Neurosciences
Saravanan Subramaniam, David T. Blake, Christos Constantinidis
Summary: DBS has emerged as a potential treatment for memory and cognitive impairment in neurodegenerative diseases. Stimulating specific brain structures, such as the nucleus basalis of Meynert, can enhance cortical activity and potentially ameliorate neuropathological mechanisms associated with Alzheimer's disease. High-frequency, continuous stimulation may not be suitable for Alzheimer's disease, and lower stimulation frequency or intermittent patterns of stimulation may be more effective when targeting the cholinergic forebrain.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Nima Khalighinejad, Sanjay Manohar, Masud Husain, Matthew F. S. Rushworth
Summary: Decision-making involves choosing actions, as well as determining when and whether to initiate them. Different brain regions, such as DRN, BF, and ACC, contribute to different stages of decision-making, with 5-HT and ACh playing complementary roles.
Review
Neurosciences
Harald Hampel, Andrea Vergallo, Filippo Caraci, A. Claudio Cuello, Pablo Lemercier, Bruno Vellas, Kelly Virecoulon Giudici, Filippo Baldacci, Britta Hanisch, Marion Haberkamp, Karl Broich, Robert Nistico, Enzo Emanuele, Francisco Llavero, Jose L. Zugaza, Alejandro Lucia, Ezio Giacobini, Simone Lista
Summary: The availability of disease-modifying therapies for Alzheimer's disease will lead to a large demand for clinical and biological screening, challenging global healthcare systems. Advancements are needed in validating and qualifying minimally-invasive blood-based biomarkers to align with an evolving ATN + classification system. Novel pathophysiological mechanisms and candidate biomarkers are being integrated into blood-based liquid biopsies to drive precision medicine strategies.
Review
Immunology
Harald Hampel, Filippo Caraci, A. Claudio Cuello, Giuseppe Caruso, Robert Nistico, Massimo Corbo, Filippo Baldacci, Nicola Toschi, Francesco Garaci, Patrizia A. Chiesa, Steven R. Verdooner, Leyla Akman-Anderson, Felix Hernandez, Jesus avila, Enzo Emanuele, Pedro L. Valenzuela, Alejandro Lucia, Mark Watling, Bruno P. Imbimbo, Andrea Vergallo, Simone Lista
FRONTIERS IN IMMUNOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Rowan Pentz, M. Florencia Iulita, Adriana Ducatenzeiler, David A. Bennett, A. Claudio Cuello
Summary: The study revealed that in Alzheimer's disease, there are changes in the metabolism of NGF, leading to disease progression. Mature NGF degradation is enhanced while proNGF maturation is impaired, with these changes correlating with cognition, pathology, and cholinergic tone.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Min Su Kang, Arturo Aliaga Aliaga, Monica Shin, Sulantha Mathotaarachchi, Andrea L. Benedet, Tharick A. Pascoal, Joseph Therriault, Mira Chamoun, Melissa Savard, Gabriel A. Devenyi, Axel Mathieu, M. Mallar Chakravarty, Asa Sandelius, Kaj Blennow, Henrik Zetterberg, Jean-Paul Soucy, A. Claudio Cuello, Gassan Massarweh, Serge Gauthier, Pedro Rosa-Neto
Summary: The study found that increased NFL concentrations in cerebrospinal fluid (CSF) and plasma were associated with reduced grey matter density in vulnerable brain regions in Alzheimer's disease patients and transgenic rats. These results support the utility of NFL as a neuronal injury biomarker.
MOLECULAR PSYCHIATRY
(2021)
Article
Clinical Neurology
Rowan Pentz, M. Florencia Iulita, Adriana Ducatenzeiler, Laura Videla, Bessy Benejam, Maria Carmona Iragui, Rafael Blesa, Alberto Lleo, Juan Fortea, A. Claudio Cuello
Summary: The discovery of altered NGF metabolism in Down syndrome and Alzheimer's disease brains led to the identification of NGF deregulation biomarkers in AD pathology. Monitoring NGF pathway markers in plasma and CSF can help distinguish DSAD from aDS, and these markers are associated with CSF amyloid beta and tau, varying by sex. These findings support the relevance of brain NGF metabolism changes in AD pathology and their potential use for AD staging and precision medicine in individuals with DS.
ALZHEIMERS & DEMENTIA
(2021)
Article
Neurosciences
Rowan Pentz, M. Florencia Iulita, Maya Mikutra-Cencora, Adriana Ducatenzeiler, David A. Bennett, A. Claudio Cuello
Summary: This study found that upregulation of MMP-3 in AD may contribute to NGF dysmetabolism, leading to cholinergic atrophy and cognitive deficits. Frontal cortex MMP-3 protein levels were higher in males and correlated with more AD neuropathology, markers of NGF metabolism, and lower cognitive scores in males but not in females.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Geriatrics & Gerontology
Martin Habif, Sonia Do Carmo, Maria Veronica Baez, Natalia Claudia Colettis, Magali Cecilia Cercato, Daniela Alejandra Salas, Maria Florencia Acutain, Caterina Laura Sister, Valeria Laura Berkowicz, Maria Pilar Canal, Tomas Gonzalez Garello, A. Claudio Cuello, Diana Alicia Jerusalinsky
Summary: Evidence suggests that McGill-R-Thy1-APP transgenic rats exhibit significant deficits in long-term memory functions, particularly in inhibitory avoidance, novel object recognition, and social behavior, at pre-plaque early stages of Alzheimer's disease pathology. Additionally, increased transcript levels of genes related to synaptic plasticity, learning, and memory processing in the hippocampus were observed in these rats.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Psychiatry
Andrea Vergallo, Simone Lista, Yuhai Zhao, Pablo Lemercier, Stefan J. Teipel, Marie-Claude Potier, Marie-Odile Habert, Bruno Dubois, Walter J. Lukiw, Harald Hampel
Summary: The study identified brain-enriched miRNAs in a cohort of cognitively normal individuals with subjective memory complaints. It investigated the impact of age, sex, and the APOE epsilon 4 allele on miRNA plasma concentrations and explored associations with brain metabolic uptake using PET imaging. The results suggest potential associations between miRNA concentrations and neuroimaging biomarkers of AD pathophysiology.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Chemistry, Multidisciplinary
Maria Eugenia Navas Guimaraes, Roi Lopez-Blanco, Juan Correa, Marcos Fernandez-Villamarin, Maria Beatriz Bistue, Pamela Martino-Adami, Laura Morelli, Vijay Kumar, Michael F. Wempe, A. C. Cuello, Eduardo Fernandez-Megia, Martin A. Bruno
Summary: The study presents a method for delivering DMHCA using a polymer therapeutic, which effectively reduces Aβ oligomers levels in the brain of Alzheimer's disease model mice, preventing memory deterioration without affecting blood lipid levels. These results demonstrate a promising approach for potential clinical developments of DMHCA delivery systems.
Article
Biochemistry & Molecular Biology
Liudmila Sosulina, Manuel Mittag, Hans-Ruediger Geis, Kerstin Hoffmann, Igor Klyubin, Yingjie Qi, Julia Steffen, Detlef Friedrichs, Niklas Henneberg, Falko Fuhrmann, Daniel Justus, Kevin Keppler, A. Claudio Cuello, Michael J. Rowan, Martin Fuhrmann, Stefan Remy
Summary: The study found that increased intrinsic excitability of CA1 neurons in early stages of Alzheimer's disease may precede inhibitory dysfunction in disease progression.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Endocrinology & Metabolism
Min Su Kang, Monica Shin, Julie Ottoy, Arturo Aliaga Aliaga, Sulantha Mathotaarachchi, Kely Quispialaya, Tharick A. Pascoal, D. Louis Collins, M. Mallar Chakravarty, Axel Mathieu, Asa Sandelius, Kaj Blennow, Henrik Zetterberg, Gassan Massarweh, Jean-Paul Soucy, A. Claudio Cuello, Serge Gauthier, Michael Waterston, Nathan Yoganathan, Etienne Lessard, Arsalan Haqqani, Kerry Rennie, Danica Stanimirovic, Balu Chakravarthy, Pedro Rosa-Neto
Summary: This study utilized in vivo longitudinal study design and a variety of biomarkers to evaluate the efficacy of a novel brain-penetrating anti-amyloid fusion protein treatment in a transgenic rat model of Alzheimer's disease. The treatment significantly reduced brain amyloid-beta levels and improved related biomarkers.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2022)
Article
Immunology
Lisi Flores-Aguilar, M. Florencia Iulita, Chiara Orciani, Neil Tanna, Jingyun Yang, David A. Bennett, A. Claudio Cuello
Summary: Elderly individuals with amyloid-beta neuropathology but no symptomatic manifestation of dementia show cognitive decline and increased brain cytokine expression. Increased cytokine expression may be an early event in the Alzheimer's continuum. Individuals with cortical amyloid-beta deposition displayed deficits and a faster rate of cognitive decline in perceptual speed compared to those without amyloid-beta.
JOURNAL OF NEUROINFLAMMATION
(2021)
Biographical-Item
Multidisciplinary Sciences
A. Claudio Cuello
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Geriatrics & Gerontology
Sonia Do Carmo, Benjamin Kannel, A. Claudio Cuello
Summary: NGF plays a crucial role in Alzheimer's disease and Down syndrome, with disruptions in its metabolic pathway potentially leading to atrophy of the basal forebrain cholinergic system.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Chiara Orciani, Helene Hall, Rowan Pentz, Morgan K. Foret, Sonia Do Carmo, Augusto Claudio Cuello
Summary: The destruction of cholinergic nuclei in the basal forebrain can impair cognition and reduce cortical neuron markers, while also affecting brain-derived neurotrophic factor (BDNF) levels, but not nerve growth factor (NGF) levels.
JOURNAL OF NEUROCHEMISTRY
(2022)