Article
Biochemistry & Molecular Biology
Yoo Hyun Um, Sheng-Min Wang, Dong Woo Kang, Sunghwan Kim, Chang Uk Lee, Donghyeon Kim, Yeong Sim Choe, Regina E. Y. Kim, Soyoung Lee, Hyun Kook Lim
Summary: Recent studies have found that locus coeruleus (LC) and salience network (SN) functional connectivity changes play a crucial role in the early stage of Alzheimer's disease (AD), and sex is also associated with AD pathology. This study aimed to demonstrate the sex-related disparities in the functional connectivity of the SN and LC in preclinical AD. The findings suggest that there are differential patterns of LC and SN functional connectivity in males and females with preclinical AD, which interact with regional Aβ deposition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Clinical Neurology
Billie J. Matchett, Lea T. Grinberg, Panos Theofilas, Melissa E. Murray
Summary: The locus coeruleus plays a crucial role in Alzheimer's disease, with degeneration of its neurons contributing to dysregulation of neuroprotection and exacerbating pathology. Preserving the LC-NE system could be a potential therapeutic target for AD and other neurodegenerative diseases affected by LC degeneration.
ACTA NEUROPATHOLOGICA
(2021)
Article
Clinical Neurology
Neus Falgas, Isabel E. Allen, Salvatore Spina, Harli Grant, Stefanie D. Pina Escudero, Jennifer Merrilees, Rosalie Gearhart, Howard J. Rosen, Joel H. Kramer, William W. Seeley, Thomas C. Neylan, Bruce L. Miller, Gil D. Rabinovici, Lea T. Grinberg, Christine M. Walsh
Summary: In a cohort with biomarker/postmortem-confirmed diagnoses, neuropsychiatric symptoms are more severe in early-onset Alzheimer's disease (EOAD) compared to late-onset Alzheimer's disease (LOAD), with anxiety, night-time behaviors, and motor disturbances being more prominent in EOAD. There are no differences between amnestic/non-amnestic diagnoses, but co-pathologies such as argyrophilic grain disease in LOAD may contribute to increased neuropsychiatric symptoms.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Review
Clinical Neurology
Camille Malatt, Michele Tagliati
Summary: This review provides an update on the current understanding of the neuropathological processes affecting the locus coeruleus/norepinephrine (LC/NE) system and their impact on the symptomatology of Alzheimer's disease and Parkinson's disease. It also explores therapeutic actions targeting the noradrenergic system. Recent studies have shown that locus coeruleus degeneration and/or hyperactivation play an early role in the neurodegenerative process, including triggering neuroinflammation. Nonmotor and noncognitive symptoms, associated with the involvement of the LC/NE system, have become increasingly important in the definition and treatment of these diseases. The diverse symptomatology of Alzheimer's disease and Parkinson's disease suggests a multisystem neurodegenerative process, with the LC/NE system playing a key role in its initiation and maintenance.
CURRENT OPINION IN NEUROLOGY
(2022)
Article
Clinical Neurology
Allan I. Levey, Deqiang Qiu, Liping Zhao, William T. Hu, Duc M. Duong, Lenora Higginbotham, Eric B. Dammer, Nicholas T. Seyfried, Thomas S. Wingo, Chadwick M. Hales, Malu Gamez Tansey, David S. Goldstein, Anees Abrol, Vince D. Calhoun, Felicia C. Goldstein, Ihab Hajjar, Anne M. Fagan, Doug Galasko, Steven D. Edland, John Hanfelt, James J. Lah, David Weinshenker
Summary: The study demonstrated that atomoxetine, a clinically approved noradrenaline reuptake inhibitor, improved multiple Alzheimer's disease biomarkers in individuals with mild cognitive impairment. Treatment with atomoxetine significantly reduced CSF levels of Tau and pTau, normalized CSF protein biomarker panels linked to synaptic function, brain metabolism, and glial immunity, and increased brain activity and metabolism in key temporal lobe circuits.
Article
Neurosciences
Meng Li, Shanwen Liu, Hongqin Zhu, Zhiwen Guo, Yuqi Zhi, Rong Liu, Zhen Jiang, Xiaoyun Liang, Hua Hu, Jiangtao Zhu
Summary: The study utilized NM-MRI technique to investigate LC signal changes in AD patients, revealing a significant correlation between LC-CRs and cognitive function in AD group. Specifically, LC-CRs showed significant positive correlation with MMSE sub item Drawing in AD group and MoCA sub item Attention in MCI group.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Neurosciences
Mariane C. Vicente, Angelita M. Stabile, Mateus Amorim, Conceicao E. Anibal Silva, Luis Gustavo A. Patrone, Thiago M. Cunha, Kenia C. Bicego, Maria C. Almeida, Daniel C. Carrettiero, Luciane H. Gargaglioni
Summary: This study found that minocycline treatment effectively reduces neuroinflammation and improves cognitive function, as well as restores the sleep-wake pattern.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Review
Pharmacology & Pharmacy
Andrew K. Evans, Erwin Defensor, Mehrdad Shamloo
Summary: This review examines the vulnerability mechanisms of locus coeruleus noradrenergic neurons, the impact of environmental and genetic factors on their risk, and potential interventions to reduce degeneration of these neurons.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Neurosciences
Michael A. Kelberman, Claire R. Anderson, Eli Chlan, Jacki M. Rorabaugh, Katharine E. McCann, David Weinshenker
Summary: This study investigated the effects of hyperphosphorylated tau on AD-related neuropathology and behavior using TgF344-AD rats and WT rats as well as relevant viral models. The results showed that the effects of hyperphosphorylated tau on AD-like neuropathology and behavioral symptoms were subtle.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Review
Biochemistry & Molecular Biology
Irene L. Gutierrez, Cinzia Dello Russo, Fabiana Novellino, Javier R. Caso, Borja Garcia-Bueno, Juan C. Leza, Jose L. M. Madrigal
Summary: This article summarizes the role of noradrenaline in Alzheimer's disease and suggests the use of noradrenaline-modulating drugs as a therapeutic option.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Ruihua Hou, Rebecca Beardmore, Clive Holmes, Clive Osmond, Angela Darekar
Summary: This study is the largest individually-matched case-control study to visualize the locus coeruleus degeneration in Alzheimer's disease patients, revealing significant LC degeneration which holds promise for stratifying patients for treatment targeting noradrenergic dysfunction.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2021)
Review
Biology
Dilek Mercan, Michael Thomas Heneka
Summary: This article summarizes the important contribution of Locus coeruleus degeneration to the pathogenic progression of Alzheimer's disease (AD). Degeneration of LC leads to decreased noradrenaline levels, causing increased neuroinflammation, enhanced amyloid and tau burden, as well as impairment in cognition and synaptic plasticity.
Article
Clinical Neurology
Maxime Van Egroo, Roy W. E. van Hooren, Heidi I. L. Jacobs
Summary: Our study found that poorer LC structural integrity is associated with increased frequency of nocturnal awakenings in the context of AD, especially in individuals with elevated plasma total tau levels.
ALZHEIMERS RESEARCH & THERAPY
(2021)
Article
Clinical Neurology
Heidi I. L. Jacobs, John Alex Becker, Kenneth Kwong, Diana Munera, Liliana Ramirez-Gomez, Nina Engels-Dominguez, Justin S. Sanchez, Clara Vila-Castelar, Ana Baena, Reisa A. Sperling, Keith A. Johnson, Francisco Lopera, Yakeel T. Quiroz
Summary: LC integrity is a marker of disease progression in preclinical ADAD.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Whitney Marilyn Freeze, Susanne Janneke Van Veluw, Willemijn Josepha Jansen, David Alan Bennett, Heidi Irma Louisa Jacobs
Summary: This study investigated the link between locus coeruleus (LC) pathology and cerebral microangiopathy in two large neuropathology datasets. The findings suggest that LC pathology is associated with cerebral amyloid angiopathy and arteriolosclerosis, indicating a potential role of LC degeneration in the pathways relating vascular pathology to Alzheimer's disease.
ALZHEIMERS & DEMENTIA
(2023)