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
Yin Xu, Nicholas E. Propson, Shuqi Du, Wen Xiong, Hui Zheng
Summary: Studies indicate that microglial-specific autophagy, represented by Atg7, plays a crucial role in regulating lipid metabolism and neuroinflammation. Deletion of Atg7 in microglia leads to a proinflammatory status and exacerbates intraneuronal tau pathology.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Lea L. Weston, Shanya Jiang, Devon Chisholm, Lauren L. Jantzie, Kiran Bhaskar
Summary: The study revealed that genetic deletion of IL-10 exacerbates neuroinflammation and tau phosphorylation, leading to neurodegeneration. Loss of IL-10 activates microglia, enhances IL-6 expression, and results in increased phosphorylation of tau protein under acute systemic inflammation.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Neurosciences
Rinie Bajracharya, David Brici, Liviu-Gabriel Bodea, Phillip W. Janowicz, Jurgen Gotz, Rebecca M. Nisbet
Summary: The study compared the efficacy of tau-specific antibodies with different Fc-receptor binding affinities in reducing tau pathology and microgliosis in an AD mouse model. The results showed that the IgG1/kappa isoform had a better ability to reduce tau pathology and microgliosis, while the IgG2a/kappa isoform enhanced extracellular tau phagocytosis in vitro.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Neurosciences
Bing Zhu, Yan Liu, Spring Hwang, Kailey Archuleta, Huijie Huang, Alex Campos, Rabi Murad, Juan Pina-Crespo, Huaxi Xu, Timothy Y. Huang
Summary: This study found that Trem2 deletion can enhance the spreading of tau in the brain of mice, leading to impaired synaptic function and memory. Furthermore, Trem2 deletion can strengthen the ability of microglia to transmit tau through exosomal vesicles.
MOLECULAR NEURODEGENERATION
(2022)
Review
Neurosciences
Guimei Zhang, Zicheng Wang, Huiling Hu, Meng Zhao, Li Sun
Summary: Alzheimer's disease is a common type of age-related dementia, where dysregulated microglia activity can lead to chronic neuroinflammation, promote pathological protein accumulation, and impair mitophagy. Targeting microglia may offer new therapeutic interventions for the disease.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Neurosciences
Juan R. Perea, Marta Bolos, Raquel Cuadros, Esther Garcia, Vega Garcia-Escudero, Felix Hernandez, Roisin M. McManus, Michael T. Heneka, Jesus Avila
Summary: This study demonstrates that inhibiting p38 can attenuate the toxic effect of tau in microglia and enhance microglia-mediated tau phagocytosis.
MOLECULAR NEUROBIOLOGY
(2022)
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)
Review
Immunology
Yijun Chen, Yang Yu
Summary: Alzheimer's Disease (AD) is mostly responsible for dementia, characterized by neuritic plaques and neurofibrillary tangles containing aggregated β-amyloid (Aβ) and hyperphosphorylated tau protein. Recent focus has been on disease-modifying therapy targeting Aβ, although the efficacy and long-term safety of such drugs are still controversial. Tau has gained attention as a therapeutic target due to its association with cognitive dysfunction. Inflammation, especially neuroinflammation, is linked to AD and tau pathology. Understanding the relationship between tau pathology and neuroinflammation will contribute to discovering therapeutic targets for AD and other tau-related diseases.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Neurosciences
Lu Wang, Yingjuan Wei, Zhenzhou Sun, Lin-Hua Jiang, Yaling Yin, Panpan Zheng, Yun Fu, Hongwei Wang, Changzheng Li, Jian-Zhi Wang
Summary: Tau protein hyperphosphorylation and NFTs formation are key features of AD, and DpdtpA can attenuate these processes by regulating the PI3K/AKT/GSK-36 signaling pathway. DpdtpA also reduces microglial activation and inflammatory responses induced by Tau, offering a potential treatment option for AD-associated neuroinflammation.
Article
Neurosciences
Julia Klein, Xinyu Yan, Aubrey Johnson, Zeljko Tomljanovic, James Zou, Krista Polly, Lawrence S. Honig, Adam M. Brickman, Yaakov Stern, D. P. Devanand, Seonjoo Lee, William C. Kreisl
Summary: Olfactory identification deficits are closely related to the extent of tau pathology and neuroinflammation, particularly in patients with amyloid pathophysiology. Amyloid positivity and cognitive status have independent effects on UPSIT performance. Low UPSIT performance may be a marker for AD pathophysiology in cognitively normal individuals.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Cell Biology
Audrey Lee-Gosselin, Nur Jury-Garfe, Yanwen You, Luke Dabin, Disha Soni, Sayan Dutta, Jean-Christophe Rochet, Jungsu Kim, Adrian L. Oblak, Cristian A. Lasagna-Reeves
Summary: The study investigated the effects of TREM2 deficiency on tau spreading using a mouse model and found that Trem2(-/-) mice showed attenuated tau pathology in multiple brain regions along with decreased microglial density. The reduced TREM2 signaling impaired microglia activation and their contribution to tau spreading. However, caution should be exercised before targeting TREM2 as a therapeutic entry point for Alzheimer's disease until its involvement in tau aggregation and propagation is better understood.
Article
Cell Biology
Chinmaya Panda, Clara Voelz, Pardes Habib, Christian Mevissen, Thomas Pufe, Cordian Beyer, Sharad Gupta, Alexander Slowik
Summary: This study demonstrates that aggregated PHF6 peptide upregulates NLRP3 inflammasome expression and induces IL-1β and IL-18 expression in HMC3 cells, as well as affecting other inflammation and microglial polarization markers. Furthermore, the aggregated PHF6 also influences Beclin-1 expression and autophagy in a time-dependent manner. Overall, the study provides insights into the complex interplay between Alzheimer's PHF6 peptide aggregation and microglial inflammation, polarization, and autophagy.
Article
Immunology
Zhi-Bo Wang, Ya-Hui Ma, Yan Sun, Lan Tan, Hui-Fu Wang, Jin-Tai Yu
Summary: This study found that interleukin-3 (IL-3) secreted by astrocytes is associated with soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and mediates the correlation between A beta pathology and tau pathology in Alzheimer's disease (AD). IL-3 may play a crucial role in the spread from A beta pathology to tau pathology to cognitive impairment.
JOURNAL OF NEUROINFLAMMATION
(2022)
Review
Biochemistry & Molecular Biology
Ziyad M. Althafar
Summary: This study summarizes the molecular pathogenesis of Alzheimer's disease (AD), the activities of microglia in the adult brain, the role of microglia in the aging brain, and the significance of targeting microglia for the treatment of AD.
Article
Neurosciences
Sarah L. DeVos, Bianca T. Corjuc, Derek H. Oakley, Chloe K. Nobuhara, Riley N. Bannon, Alison Chase, Caitlin Commins, Jose A. Gonzalez, Patrick M. Dooley, Matthew P. Frosch, Bradley T. Hyman
FRONTIERS IN NEUROSCIENCE
(2018)
Article
Oncology
K. Ina Ly, Derek H. Oakley, Alexander B. Pine, Matthew P. Frosch, Sy Han Chiou, Rebecca A. Betensky, Stuart R. Pomerantz, Fred H. Hochberg, Tracy T. Batchelor, Daniel P. Cahill, Jorg Dietrich
Article
Medicine, General & Internal
Charles C. Hardin, Rajeev Malhotra, Milena Petranovic, Sheila Klassen, Nino Mihatov, Derek H. Oakley
NEW ENGLAND JOURNAL OF MEDICINE
(2019)
Article
Clinical Neurology
Jaeho Hwang, Anna M. Bank, Farzad Mortazavi, Derek H. Oakley, Matthew P. Frosch, Jeremy D. Schmahmann
Review
Neurosciences
Sarah C. Hopp
Summary: This review explores the potential of L-VDCCs as a target for treating CNS disorders, with a focus on their role in microglia. Microglia play a crucial role in the inflammatory response in various CNS diseases, making the calcium signaling pathway a valuable target for manipulation.
JOURNAL OF NEUROSCIENCE RESEARCH
(2021)
Article
Clinical Neurology
Derek H. Oakley, Mirra Chung, Naomi Klickstein, Caitlin Commins, Bradley T. Hyman, Matthew P. Frosch
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2020)
Article
Biochemistry & Molecular Biology
Simon Dujardin, Caitlin Commins, Aurelien Lathuiliere, Pieter Beerepoot, Analiese R. Fernandes, Tarun Kamath, Mark B. De Los Santos, Naomi Klickstein, Diana L. Corjuc, Bianca T. Corjuc, Patrick M. Dooley, Arthur Viode, Derek H. Oakley, Benjamin D. Moore, Kristina Mullin, Dinorah Jean-Gilles, Ryan Clark, Kevin Atchison, Renee Moore, Lori B. Chibnik, Rudolph E. Tanzi, Matthew P. Frosch, Alberto Serrano-Pozo, Fiona Elwood, Judith A. Steen, Matthew E. Kennedy, Bradley T. Hyman
Article
Medicine, General & Internal
Christian Mueller, James D. Berry, Diane M. McKenna-Yasek, Gwladys Gernoux, Margaret A. Owegi, Lindsay M. Pothier, Catherine L. Douthwright, Dario Gelevski, Sarah D. Luppino, Meghan Blackwood, Nicholas S. Wightman, Derek H. Oakley, Matthew P. Frosch, Terrence R. Flotte, Merit E. Cudkowicz, Robert H. Brown
NEW ENGLAND JOURNAL OF MEDICINE
(2020)
Article
Neurosciences
Derek H. Oakley, Naomi Klickstein, Caitlin Commins, Mirra Chung, Simon Dujardin, Rachel E. Bennett, Bradley T. Hyman, Matthew P. Frosch
Summary: This study established an accelerated human neuronal model incorporating soluble tau species and tau aggregation, and showed that uptake of exogenous tau seeds increases the risk of neuronal death. Specific morphologic strains of Tau aggregation were identified to be associated with differing levels of neurotoxicity. Additionally, iPSC neurons expressing the PSEN1 L435F mutation exhibited accelerated Tau aggregation kinetics and a bias in tau strain propagation.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Jessica L. Wickline, Sabrina Smith, Riley Shin, Kristian Odfalk, Jesse Sanchez, Martin Javors, Brett Ginsburg, Sarah C. Hopp
Summary: Epidemiological studies suggest that L-type calcium channel antagonists may reduce the incidence of age-associated neurodegenerative diseases, including Alzheimer's disease. However, the protective mechanism of LTCC antagonists is unknown.
Article
Neurosciences
Kristian F. Odfalk, Jessica L. Wickline, Sabrina Smith, Radek Dobrowolski, Sarah C. Hopp
Summary: Dysfunction of the endosomal-lysosomal network is a notable feature of Alzheimer's disease, and TMEM55B may play a role in reducing this dysfunction.
Article
Clinical Neurology
Tarun Kamath, Naomi Klickstein, Caitlin Commins, Analiese R. Fernandes, Derek H. Oakley, Matthew P. Frosch, Bradley T. Hyman, Simon Dujardin
Summary: The accumulation of tau aggregates in tauopathies display "prion-like" behavior, with differences in structures among different conditions. Recent studies have shown biochemical and bioactive differences in tau species among individuals with sporadic Alzheimer's disease. Live-cell imaging revealed a consistent aggregation pattern with distinct parameters, including lag phase and growth phase, dependent on seeding-competent tau concentration. The kinetics of aggregation may reflect underlying structural differences in tau aggregates, confirming heterogeneity in tau proteopathic seeds among Alzheimer's disease patients.
BRAIN COMMUNICATIONS
(2021)
Meeting Abstract
Clinical Neurology
Derek Oakley, Naomi Klickstein, Bradley Hyman, Matthew Frosch
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2018)