Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are two fatal neurodegenerative disorders with considerable clinical, pathological and genetic overlap. Both disorders are chara...
Authors: Ali Jawaid, Romesa Khan, Magdalini Polymenidou and Paul E. Schulz
Although diabetic retinopathy (DR) has long been considered as a microvascular disorder, mounting evidence suggests that diabetic retinal neurodegeneration, in particular synaptic loss and dysfunction of retin...
Neuroinflammation is a hallmark of neurodegenerative disease and a significant component of the pathology of Alzheimer’s disease (AD). Patients present with extensive microgliosis along with elevated pro-infla...
Authors: Aaron D. Thome, Alireza Faridar, David R. Beers, Jason R. Thonhoff, Weihua Zhao, Shixiang Wen, Belen Pascual, Joseph C. Masdeu and Stanley H. Appel
It is unclear to what extent pre-clinical studies in genetically homogeneous animal models of amyotrophic lateral sclerosis (ALS), an invariably fatal neurodegenerative disorder, can be informative of human pa...
Authors: Irene Zubiri, Vittoria Lombardi, Michael Bremang, Vikram Mitra, Giovanni Nardo, Rocco Adiutori, Ching-Hua Lu, Emanuela Leoni, Ping Yip, Ozlem Yildiz, Malcolm Ward, Linda Greensmith, Caterina Bendotti, Ian Pike and Andrea Malaspina
Alzheimer’s disease (AD) and related tauopathies are neurodegenerative diseases that are characterized by the presence of insoluble inclusions of the protein tau within brain neurons and often glia. Tau is nor...
Authors: Bin Zhang, Yuemang Yao, Anne-Sophie Cornec, Killian Oukoloff, Michael J. James, Pyry Koivula, John Q. Trojanowski, Amos B. Smith III, Virginia M.-Y. Lee, Carlo Ballatore and Kurt R. Brunden
Clearance at the blood-brain barrier (BBB) plays an important role in removal of Alzheimer’s amyloid-β (Aβ) toxin from brain both in humans and animal models. Apolipoprotein E (apoE), the major genetic risk fa...
Authors: Qingyi Ma, Zhen Zhao, Abhay P Sagare, Yingxi Wu, Min Wang, Nelly Chuqui Owens, Philip B Verghese, Joachim Herz, David M Holtzman and Berislav V Zlokovic
Mitochondrial dysfunction has been implicated in the pathologies of a number of retinal degenerative diseases in both the outer and inner retina. In the outer retina, photoreceptors are particularly vulnerable...
Authors: Takae Kiyama, Ching-Kang Chen, Steven W Wang, Ping Pan, Zhenlin Ju, Jing Wang, Shinako Takada, William H Klein and Chai-An Mao
TAR DNA binding protein 43 (TDP-43) is the main disease protein in most patients with amyotrophic lateral sclerosis (ALS) and about 50% of patients with frontotemporal dementia (FTD). TDP-43 pathology is not r...
Authors: Sander Beel, Sarah Herdewyn, Raheem Fazal, Mathias De Decker, Matthieu Moisse, Wim Robberecht, Ludo Van Den Bosch and Philip Van Damme
Despite diverging levels of amyloid-β (Aβ) and TAU pathology, different mouse models, as well as sporadic AD patients show predictable patterns of episodic memory loss. MicroRNA (miRNA) deregulation is well es...
Authors: Annerieke Sierksma, Ashley Lu, Evgenia Salta, Elke Vanden Eynden, Zsuzsanna Callaerts-Vegh, Rudi D’Hooge, David Blum, Luc Buée, Mark Fiers and Bart De Strooper
Rare coding variants ABI3_rs616338-T and PLCG2_rs72824905-G were identified as risk or protective factors, respectively, for Alzheimer’s disease (AD).
Authors: Olivia J Conway, Minerva M Carrasquillo, Xue Wang, Jenny M Bredenberg, Joseph S Reddy, Samantha L Strickland, Curtis S Younkin, Jeremy D Burgess, Mariet Allen, Sarah J Lincoln, Thuy Nguyen, Kimberly G Malphrus, Alexandra I Soto, Ronald L Walton, Bradley F Boeve, Ronald C Petersen…
The complicated cellular and biochemical changes that occur in brain during Alzheimer’s disease are poorly understood. In a previous study we used an unbiased label-free quantitative mass spectrometry-based pr...
Authors: Erik C. B. Johnson, Eric B. Dammer, Duc M. Duong, Luming Yin, Madhav Thambisetty, Juan C. Troncoso, James J. Lah, Allan I. Levey and Nicholas T. Seyfried
Alzheimer’s disease (AD) represents an urgent public health mandate. AD is no longer considered a neural-centric disease; rather, a plethora of recent studies strongly implicate a critical role played by neuro...
Neuronal Ca2+ dyshomeostasis and hyperactivity play a central role in Alzheimer’s disease pathology and progression. Amyloid-beta together with non-genetic risk-factors of Alzheimer’s disease contributes to incre...
Authors: Michael Dumbacher, Tom Van Dooren, Katrien Princen, Koen De Witte, Mélissa Farinelli, Sam Lievens, Jan Tavernier, Wim Dehaen, Stefaan Wera, Joris Winderickx, Sara Allasia, Amuri Kilonda, Stéphane Spieser, Arnaud Marchand, Patrick Chaltin, Casper C. Hoogenraad…
The R47H variant of the Triggering Receptor Expressed on Myeloid cells 2 (TREM2) significantly increases the risk for late onset Alzheimer’s disease. Mouse models accurately reproducing phenotypes observed in ...
Authors: Xianyuan Xiang, Thomas M. Piers, Benedikt Wefers, Kaichuan Zhu, Anna Mallach, Bettina Brunner, Gernot Kleinberger, Wilbur Song, Marco Colonna, Jochen Herms, Wolfgang Wurst, Jennifer M. Pocock and Christian Haass
Heterozygous loss-of-function mutations in the progranulin gene (GRN) lead to frontotemporal lobar degeneration (FTLD) while the complete loss of progranulin (PGRN) function results in neuronal ceroid lipofuscino...
Authors: Julia K. Götzl, Alessio-Vittorio Colombo, Katrin Fellerer, Anika Reifschneider, Georg Werner, Sabina Tahirovic, Christian Haass and Anja Capell
Neurogranin (Ng) is a small 7.6 kDa postsynaptic protein that has been detected at elevated concentrations in cerebrospinal fluid (CSF) of patients with Alzheimer’s disease (AD), both as a full-length molecule...
Authors: Bruno Becker, Faisal Hayat Nazir, Gunnar Brinkmalm, Elena Camporesi, Hlin Kvartsberg, Erik Portelius, Martina Boström, Marie Kalm, Kina Höglund, Maria Olsson, Henrik Zetterberg and Kaj Blennow
Many neurodegenerative diseases are caused by nucleotide repeat expansions, but most expansions, like the C9orf72 ‘GGGGCC’ (G4C2) repeat that causes approximately 5–7% of all amyotrophic lateral sclerosis (ALS) a...
Authors: Mark T. W. Ebbert, Stefan L. Farrugia, Jonathon P. Sens, Karen Jansen-West, Tania F. Gendron, Mercedes Prudencio, Ian J. McLaughlin, Brett Bowman, Matthew Seetin, Mariely DeJesus-Hernandez, Jazmyne Jackson, Patricia H. Brown, Dennis W. Dickson, Marka van Blitterswijk, Rosa Rademakers, Leonard Petrucelli…
The role of the alternative complement pathway and its mediation by retinal microglia and macrophages, is well-established in the pathogenesis of Age-Related Macular Degeneration (AMD). However, the contributi...
Authors: Haihan Jiao, Matt Rutar, Nilisha Fernando, Ted Yednock, Sethu Sankaranarayanan, Riemke Aggio-Bruce, Jan Provis and Riccardo Natoli
Microglia play critical roles in the brain during homeostasis and pathological conditions. Understanding the molecular events underpinning microglial functions and activation states will further enable us to t...
Authors: Justin Rustenhoven, Amy M. Smith, Leon C. Smyth, Deidre Jansson, Emma L. Scotter, Molly E. V. Swanson, Miranda Aalderink, Natacha Coppieters, Pritika Narayan, Renee Handley, Chris Overall, Thomas I. H. Park, Patrick Schweder, Peter Heppner, Maurice A. Curtis, Richard L. M. Faull…
The major histocompatibility complex I (MHCI) is a key molecule for the interaction of mononucleated cells with CD8+T lymphocytes. We previously showed that MHCI is upregulated in the spinal cord microglia and mo...
Authors: Giovanni Nardo, Maria Chiara Trolese, Mattia Verderio, Alessandro Mariani, Massimiliano de Paola, Nilo Riva, Giorgia Dina, Nicolò Panini, Eugenio Erba, Angelo Quattrini and Caterina Bendotti
Synucleinopathies of the aging population are an heterogeneous group of neurological disorders that includes Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) and are characterized by the progressiv...
Authors: Changyoun Kim, Brian Spencer, Edward Rockenstein, Hodaka Yamakado, Michael Mante, Anthony Adame, Jerel Adam Fields, Deborah Masliah, Michiyo Iba, He-Jin Lee, Robert A. Rissman, Seung-Jae Lee and Eliezer Masliah
Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease for which the genetic contribution is incompletely understood.
Authors: Jason A. Chen, Zhongbo Chen, Hyejung Won, Alden Y. Huang, Jennifer K. Lowe, Kevin Wojta, Jennifer S. Yokoyama, Gilbert Bensimon, P. Nigel Leigh, Christine Payan, Aleksey Shatunov, Ashley R. Jones, Cathryn M. Lewis, Panagiotis Deloukas, Philippe Amouyel, Christophe Tzourio…
The combination of genetics and genomics in Parkinson´s disease has recently begun to unveil molecular mechanisms possibly underlying disease onset and progression. In particular, catabolic processes such as a...
Authors: Julia Obergasteiger, Giulia Frapporti, Peter P. Pramstaller, Andrew A. Hicks and Mattia Volta
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. About 90% of ALS cases are without a known genetic cause. The human endogenous retrovirus multi-copy HERV-K(HML-2) group was recently ...
Authors: Jens Mayer, Christian Harz, Laura Sanchez, Gavin C. Pereira, Esther Maldener, Sara R. Heras, Lyle W. Ostrow, John Ravits, Ranjan Batra, Eckart Meese, Jose Luis García-Pérez and John L. Goodier
The role of the innate immune system in Alzheimer’s disease (AD) and neurodegenerative disease susceptibility has recently been highlighted in genetic studies. However, we do not know whether risk for inflamma...
Authors: Daniel Felsky, Ellis Patrick, Julie A. Schneider, Sara Mostafavi, Chris Gaiteri, Nikolaos Patsopoulos, David A. Bennett and Philip L. De Jager
Progressive supranuclear palsy (PSP) is a parkinsonian neurodegenerative tauopathy affecting brain regions involved in motor function, including the basal ganglia, diencephalon and brainstem. While PSP is larg...
Authors: Monica Y. Sanchez-Contreras, Naomi Kouri, Casey N. Cook, Daniel J. Serie, Michael G. Heckman, NiCole A. Finch, Richard J. Caselli, Ryan J. Uitti, Zbigniew K. Wszolek, Neill Graff-Radford, Leonard Petrucelli, Li-San Wang, Gerard D. Schellenberg, Dennis W. Dickson, Rosa Rademakers and Owen A. Ross
Hereditary spastic paraplegias (HSP) is a heterogeneous group of rare neurodegenerative disorders affecting the corticospinal tracts. To date, more than 78 HSP loci have been mapped to cause HSP. However, both...
Authors: En-Lin Dong, Chong Wang, Shuang Wu, Ying-Qian Lu, Xiao-Hong Lin, Hui-Zhen Su, Miao Zhao, Jin He, Li-Xiang Ma, Ning Wang, Wan-Jin Chen and Xiang Lin
Single nucleotide polymorphisms (SNPs) inherited as one of two common haplotypes at the transmembrane protein 106B (TMEM106B) locus are associated with the risk of multiple neurodegenerative diseases, including f...
Authors: Yingxue Ren, Marka van Blitterswijk, Mariet Allen, Minerva M. Carrasquillo, Joseph S. Reddy, Xue Wang, Thomas G. Beach, Dennis W. Dickson, Nilüfer Ertekin-Taner, Yan W. Asmann and Rosa Rademakers
Microglia are innate immune cells of the brain that perform phagocytic and inflammatory functions in disease conditions. Transcriptomic studies of acutely-isolated microglia have provided novel insights into t...
Authors: Srikant Rangaraju, Eric B. Dammer, Syed Ali Raza, Tianwen Gao, Hailian Xiao, Ranjita Betarbet, Duc M. Duong, James A. Webster, Chadwick M. Hales, James J. Lah, Allan I. Levey and Nicholas T. Seyfried
Type 2 diabetes (T2D) is a recognized risk factor for the development of cognitive impairment (CI) and/or dementia, although the exact nature of the molecular pathology of T2D-associated CI remains obscure. On...
Authors: Cesar L. Moreno, Lucio Della Guardia, Valeria Shnyder, Maitane Ortiz-Virumbrales, Ilya Kruglikov, Bin Zhang, Eric E. Schadt, Rudolph E. Tanzi, Scott Noggle, Christoph Buettner and Sam Gandy
Spinocerebellar ataxia type 3 (SCA3) is a progressive neurodegenerative disorder caused by expansion of the polyglutamine repeat in the ataxin-3 protein. Expression of mutant ataxin-3 is known to result in tra...
Authors: Lodewijk J. A. Toonen, Maurice Overzier, Melvin M. Evers, Leticia G. Leon, Sander A. J. van der Zeeuw, Hailiang Mei, Szymon M. Kielbasa, Jelle J. Goeman, Kristina M. Hettne, Olafur Th. Magnusson, Marion Poirel, Alexandre Seyer, Peter A. C. ‘t Hoen and Willeke M. C. van Roon-Mom
Loss of function mutations in progranulin (GRN) are a major cause of frontotemporal dementia (FTD). Progranulin is a secreted glycoprotein that localizes to lysosomes and is critical for proper lysosomal function...
Authors: Andrew E. Arrant, Alexandra M. Nicholson, Xiaolai Zhou, Rosa Rademakers and Erik D. Roberson
Paraspeckles are subnuclear bodies assembled on a long non-coding RNA (lncRNA) NEAT1. Their enhanced formation in spinal neurons of sporadic amyotrophic lateral sclerosis (ALS) patients has been reported but u...
Authors: Tatyana A. Shelkovnikova, Michail S. Kukharsky, Haiyan An, Pasquale Dimasi, Svetlana Alexeeva, Osman Shabir, Paul R. Heath and Vladimir L. Buchman
The R47H variant of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) confers greatly increased risk for Alzheimer’s disease (AD), reflective of a central role for myeloid cells in neurodegeneration. Un...
Authors: Paul J. Cheng-Hathaway, Erin G. Reed-Geaghan, Taylor R. Jay, Brad T. Casali, Shane M. Bemiller, Shweta S. Puntambekar, Victoria E. von Saucken, Roxanne Y. Williams, J. Colleen Karlo, Miguel Moutinho, Guixiang Xu, Richard M. Ransohoff, Bruce T. Lamb and Gary E. Landreth
Several molecular pathways are currently being targeted in attempts to develop disease-modifying therapies to slow down neurodegeneration in Parkinson’s disease. Failure of cellular energy metabolism has long ...
Authors: Emmanuel Quansah, Wouter Peelaerts, J. William Langston, David K. Simon, Jerry Colca and Patrik Brundin
Neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS), affect millions of people every year and so far, there...
Authors: Eduarda G Z Centeno, Helena Cimarosti and Angela Bithell
Disease-associated-microglia (DAM) represent transcriptionally-distinct and neurodegeneration-specific microglial profiles with unclear significance in Alzheimer’s disease (AD). An understanding of heterogenei...
Authors: Srikant Rangaraju, Eric B. Dammer, Syed Ali Raza, Priyadharshini Rathakrishnan, Hailian Xiao, Tianwen Gao, Duc M. Duong, Michael W. Pennington, James J. Lah, Nicholas T. Seyfried and Allan I. Levey
Huntington Disease (HD) is an incurable autosomal dominant neurodegenerative disorder driven by an expansion repeat giving rise to the mutant huntingtin protein (mHtt), which is known to disrupt a multitude of...
Authors: Rebecca Kusko, Jennifer Dreymann, Jermaine Ross, Yoonjeong Cha, Renan Escalante-Chong, Marta Garcia-Miralles, Liang Juin Tan, Michael E. Burczynski, Ben Zeskind, Daphna Laifenfeld, Mahmoud Pouladi, Michal Geva, Iris Grossman and Michael R. Hayden
Administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) increases regulatory T cell (Treg) number and function with control of neuroinflammation and neuronal protection in the 1-methyl-4-ph...
Authors: Charles R. Schutt, Howard E. Gendelman and R. Lee Mosley
Prior studies in C. elegans demonstrated that the expression of aggregation-prone polyglutamine proteins in muscle wall cells compromised the folding of co-expressed temperature-sensitive proteins, prompting inte...
Authors: Michael C. Pace, Guilian Xu, Susan Fromholt, John Howard, Benoit I. Giasson, Jada Lewis and David R. Borchelt
Extracellular aggregation of the amyloid-β (Aβ) peptide into toxic multimers is a key event in Alzheimer’s disease (AD) pathogenesis. Aβ aggregation is concentration-dependent, with higher concentrations of Aβ...
Authors: Jane C. Hettinger, Hyo Lee, Guojun Bu, David M. Holtzman and John R. Cirrito
Intraneuronal α-synuclein (α-Syn) aggregates known as Lewy bodies (LBs) and the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) are the pathological hallmarks of Parkinson’s disease (...
Authors: Norihito Uemura, Hisashi Yagi, Maiko T. Uemura, Yusuke Hatanaka, Hodaka Yamakado and Ryosuke Takahashi
Neurodegenerative diseases are a growing burden in modern society, thus crucially calling for the development of accurate diagnostic strategies. These diseases are currently incurable, a fact which has been at...
Authors: Maria Paraskevaidi, Pierre L. Martin-Hirsch and Francis L. Martin
Retinitis pigmentosa (RP) is a group of hereditary retinal neurodegenerative conditions characterized by primary dysfunction and death of photoreceptor cells, resulting in visual loss and, eventually, blindnes...
Authors: Alonso Sánchez-Cruz, Beatriz Villarejo-Zori, Miguel Marchena, Josefa Zaldivar-Díez, Valle Palomo, Carmen Gil, Ignacio Lizasoain, Pedro de la Villa, Ana Martínez, Enrique J. de la Rosa and Catalina Hernández-Sánchez
Proteolytic processing of the prion protein (PrPC) by endogenous proteases generates bioactive membrane-bound and soluble fragments which may help to explain the pleiotropic roles of this protein in the nervous s...
Authors: Luise Linsenmeier, Behnam Mohammadi, Sebastian Wetzel, Berta Puig, Walker S. Jackson, Alexander Hartmann, Keiji Uchiyama, Suehiro Sakaguchi, Kristina Endres, Jörg Tatzelt, Paul Saftig, Markus Glatzel and Hermann C. Altmeppen
Aging is the strongest risk factor for neurodegenerative diseases and extended age results in neuronal degeneration and functional decline in the visual system. Among many contributing factors to age-related d...
Authors: Todd McLaughlin, Marek Falkowski, Jae Whan Park, Stephen Keegan, Michael Elliott, Joshua J. Wang and Sarah X. Zhang
Traumatic Brain Injury (TBI) is a major cause of disability and mortality, to which there is currently no comprehensive treatment. Blood Brain Barrier (BBB) dysfunction is well documented in human TBI patients...
Authors: Bevan S. Main, Sonia Villapol, Stephanie S. Sloley, David J. Barton, Maia Parsadanian, Chinyere Agbaegbu, Kathryn Stefos, Mondona S. McCann, Patricia M. Washington, Olga C. Rodriguez and Mark P. Burns
TREM2 is an innate immune receptor specifically expressed in microglia. Coding variations in TREM2 have been reported to increase the risk for Alzheimer’s disease (AD) and other neurodegenerative diseases. Whi...
Authors: Li Zhong, Zongqi Wang, Daxin Wang, Zhe Wang, Yuka A. Martens, Linbei Wu, Ying Xu, Kai Wang, Jianguo Li, Ruizhi Huang, Dan Can, Huaxi Xu, Guojun Bu and Xiao-Fen Chen
Metabolically-obese, normal-weight (MONW) individuals are not obese in terms of weight and height but have a number of obesity-related features (e.g. greater visceral adiposity, insulin resistance, and increas...
Authors: Margalida Cifre, Andreu Palou and Paula Oliver
