Alzheimer’s disease (AD) is a globally common neurodegenerative disease, which is accompanied by alterations to various lifestyle patterns, such as sleep disturbance. The pineal gland is the primary endocrine ...
Dynactin subunit 1 is the largest subunit of the dynactin complex, an activator of the molecular motor protein complex dynein. Reduced levels of DCTN1 mRNA and protein have been found in sporadic amyotrophic late...
Authors: Valérie Bercier, Jeffrey M. Hubbard, Kevin Fidelin, Karine Duroure, Thomas O. Auer, Céline Revenu, Claire Wyart and Filippo Del Bene
Soluble aggregates of oligomeric forms of tau protein (oTau) have been associated with impairment of synaptic plasticity and memory in Alzheimer’s disease. However, the molecular mechanisms underlying the syna...
Authors: Erica Acquarone, Elentina K. Argyrousi, Manon van den Berg, Walter Gulisano, Mauro Fà, Agnieszka Staniszewski, Elisa Calcagno, Elisa Zuccarello, Luciano D’Adamio, Shi-Xian Deng, Daniela Puzzo, Ottavio Arancio and Jole Fiorito
Adult hippocampal neurogenesis plays an important role in synaptic plasticity and cogntive function. We reported that higher numbers of neural stem cells (NSC) in the hippocampus of cognitively-intact individu...
Authors: Maria-Adelaide Micci, Balaji Krishnan, Elizabeth Bishop, Wen-Ru Zhang, Jutatip Guptarak, Auston Grant, Olga Zolochevska, Batbayar Tumurbaatar, Whitney Franklin, Claudia Marino, Steven G. Widen, Arjun Luthra, Steven G. Kernie and Giulio Taglialatela
Apolipoprotein (apo) E4 is the major genetic risk factor for Alzheimer’s disease (AD), increasing risk and decreasing age of disease onset. Many studies have demonstrated the detrimental effects of apoE4 in va...
Authors: Ramsey Najm, Emily A. Jones and Yadong Huang
The Alzheimer’s disease (AD) afflicted brain is neuropathologically defined by extracellular amyloid-β (Aβ) plaques and intraneuronal neurofibrillary tangles composed of hyperphosphorylated tau protein. Howeve...
In order for Alzheimer’s disease (AD) to manifest, cells must communicate “pathogenic material” such as proteins, signaling molecules, or genetic material to ensue disease propagation. Small extracellular vesi...
Authors: Luke S. Watson, Eric D. Hamlett, Tyler D. Stone and Catrina Sims-Robinson
Currently, over five million Americans suffer with Alzheimer’s disease (AD). In the absence of a cure, this number could increase to 13.8 million by 2050. A critical goal of biomedical research is to establish...
Increasing evidence supports that cellular dysregulations in the degradative routes contribute to the initiation and progression of neurodegenerative diseases, including Alzheimer’s disease. Autophagy and endo...
Authors: Zoë P. Van Acker, Marine Bretou and Wim Annaert
Many neurodegenerative disorders, including Parkinson’s, Alzheimer’s, and amyotrophic lateral sclerosis, are well known to involve the accumulation of disease-specific proteins. Less well known are the accumul...
Low frequency coding variants in TREM2 are associated with Alzheimer disease (AD) risk and cerebrospinal fluid (CSF) TREM2 protein levels are different between AD cases and controls. Similarly, TREM2 risk variant...
Authors: Jorge L. Del-Aguila, Bruno A. Benitez, Zeran Li, Umber Dube, Kathie A. Mihindukulasuriya, John P. Budde, Fabiana H. G. Farias, Maria Victoria Fernández, Laura Ibanez, Shan Jiang, Richard J. Perrin, Nigel J. Cairns, John C. Morris, Oscar Harari and Carlos Cruchaga
Genetically modified rodent models have been valuable for investigating the pathogenesis of neurodegenerative diseases such as Parkinson’s disease (PD). Based on the fact that mutations in the PINK1 gene cause au...
Based on epidemiological and experimental studies, type 2 diabetes mellitus (T2DM), especially insulin resistance that comprises the core mechanism of T2DM, has been recognized as a significant risk factor for...
An emerging picture suggests that glial cells’ loss of beneficial roles or gain of toxic functions can contribute to neurodegenerative conditions. Among glial cells, microglia and astrocytes have been shown to...
Authors: Marie-Eve Tremblay, Mark R. Cookson and Laura Civiero
Amyotrophic lateral sclerosis (ALS) is a multifactorial fatal motoneuron disease without a cure. Ten percent of ALS cases can be pointed to a clear genetic cause, while the remaining 90% is classified as spora...
Authors: S. Beltran, M. Nassif, E. Vicencio, J. Arcos, L. Labrador, B. I. Cortes, C. Cortez, C. A. Bergmann, S. Espinoza, M. F. Hernandez, J. M. Matamala, L. Bargsted, S. Matus, D. Rojas-Rivera, M. J. M. Bertrand, D. B. Medinas…
Aggregation of tau proteins is a distinct hallmark of tauopathies and has been a focus of research and clinical trials for Alzheimer’s Disease. Recent reports have pointed towards a toxic effect of soluble or ...
Authors: Claudia Green, Astrid Sydow, Stefanie Vogel, Marta Anglada-Huguet, Dirk Wiedermann, Eckhard Mandelkow, Eva-Maria Mandelkow and Mathias Hoehn
Microglia are the principal innate immune defense cells of the centeral nervous system (CNS) and the target of the human immunodeficiency virus type one (HIV-1). A complete understanding of human microglial bi...
Authors: Saumi Mathews, Amanda Branch Woods, Ikumi Katano, Edward Makarov, Midhun B. Thomas, Howard E. Gendelman, Larisa Y. Poluektova, Mamoru Ito and Santhi Gorantla
Alzheimer’s disease is characterized by two main neuropathological hallmarks: extracellular plaques of amyloid-β (Aβ) protein and intracellular aggregates of tau protein. Although tau is normally a soluble mon...
Authors: Tirth K. Patel, LeMoyne Habimana-Griffin, Xuefeng Gao, Baogang Xu, Samuel Achilefu, Kari Alitalo, Celia A. McKee, Patrick W. Sheehan, Erik S. Musiek, Chengjie Xiong, Dean Coble and David M. Holtzman
Based on associations between sleep spindles, cognition, and sleep-dependent memory processing, here we evaluated potential relationships between levels of CSF Aβ42, P-tau, and T-tau with sleep spindle density an...
Authors: Korey Kam, Ankit Parekh, Ram A. Sharma, Andreia Andrade, Monica Lewin, Bresne Castillo, Omonigho M. Bubu, Nicholas J. Chua, Margo D. Miller, Anna E. Mullins, Lidia Glodzik, Lisa Mosconi, Nadia Gosselin, Kulkarni Prathamesh, Zhe Chen, Kaj Blennow…
A G4C2 hexanucleotide repeat expansion in the noncoding region of C9orf72 is the major genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS). Putative disease mechanisms underlyin...
Authors: Jeannie Chew, Casey Cook, Tania F. Gendron, Karen Jansen-West, Giulia del Rosso, Lillian M. Daughrity, Monica Castanedes-Casey, Aishe Kurti, Jeannette N. Stankowski, Matthew D. Disney, Jeffrey D. Rothstein, Dennis W. Dickson, John D. Fryer, Yong-Jie Zhang and Leonard Petrucelli
Neurotropic virus-based tracers have been extensively applied in mapping and manipulation of neural circuits. However, their neurotropic and neurotoxic properties remain to be fully characterized.
Authors: Leqiang Sun, Yajie Tang, Keji Yan, Jinsong Yu, Yanyan Zou, Weize Xu, Ke Xiao, Zhihui Zhang, Weiming Li, Beili Wu, Zhe Hu, Kening Chen, Zhen F. Fu, Jinxia Dai and Gang Cao
Identifying effective strategies to prevent memory loss in AD has eluded researchers to date, and likely reflects insufficient understanding of early pathogenic mechanisms directly affecting memory encoding. A...
Authors: Shreaya Chakroborty, Evan S. Hill, Daniel T. Christian, Rosalind Helfrich, Shannon Riley, Corinne Schneider, Nicolas Kapecki, Sarah Mustaly-Kalimi, Figen A. Seiler, Daniel A. Peterson, Anthony R. West, Barbara M. Vertel, William N. Frost and Grace E. Stutzmann
Glaucoma is characterized by the progressive dysfunction and loss of retinal ganglion cells. Recent work in animal models suggests that a critical neuroinflammatory event damages retinal ganglion cell axons in...
Authors: Pete A. Williams, Catherine E. Braine, Krishnakumar Kizhatil, Nicole E. Foxworth, Nicholas G. Tolman, Jeffrey M. Harder, Rebecca A. Scott, Gregory L. Sousa, Alyssa Panitch, Gareth R. Howell and Simon W. M. John
Dementia with Lewy bodies (DLB) is an age-associated neurodegenerative disorder producing progressive cognitive decline that interferes with normal life and daily activities. Neuropathologically, DLB is charac...
Authors: Tiago Fleming Outeiro, David J. Koss, Daniel Erskine, Lauren Walker, Marzena Kurzawa-Akanbi, David Burn, Paul Donaghy, Christopher Morris, John-Paul Taylor, Alan Thomas, Johannes Attems and Ian McKeith
Neuronal Ceroid Lipofuscinoses (NCLs), commonly known as Batten disease, constitute a group of the most prevalent neurodegenerative lysosomal storage disorders (LSDs). Mutations in at least 13 different genes ...
Authors: Anil B. Mukherjee, Abhilash P. Appu, Tamal Sadhukhan, Sydney Casey, Avisek Mondal, Zhongjian Zhang and Maria B. Bagh
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease of the central nervous system (CNS), which affects mostly older adults. In recent years, the incidence of PD has been dramaticall...
Uncontrolled microglial activation contributes to the pathogenesis of various neurodegenerative diseases. Previous studies have shown that proinflammatory microglia are powered by glycolysis, which relays on h...
Authors: Luxi Wang, Sofia Pavlou, Xuan Du, Mohajeet Bhuckory, Heping Xu and Mei Chen
TREM2 is a transmembrane receptor that is predominantly expressed by microglia in the central nervous system. Rare variants in the TREM2 gene increase the risk for late-onset Alzheimer’s disease (AD). Soluble TRE...
Authors: Marc Suárez-Calvet, Estrella Morenas-Rodríguez, Gernot Kleinberger, Kai Schlepckow, Miguel Ángel Araque Caballero, Nicolai Franzmeier, Anja Capell, Katrin Fellerer, Brigitte Nuscher, Erden Eren, Johannes Levin, Yuetiva Deming, Laura Piccio, Celeste M. Karch, Carlos Cruchaga, Leslie M. Shaw…
Neuronal cell loss contributes to the pathology of acute and chronic neurodegenerative diseases, including Alzheimer’s disease (AD). It remains crucial to identify molecular mechanisms sensitizing neurons to v...
Authors: Gregor Bieri, Kurt M. Lucin, Caitlin E. O’Brien, Hui Zhang, Saul A. Villeda and Tony Wyss-Coray
Microglia, the principle immune cells of the brain, play important roles in neuronal development, homeostatic function and neurodegenerative disease. Recent genetic studies have further highlighted the importa...
Authors: Amanda McQuade, Morgan Coburn, Christina H. Tu, Jonathan Hasselmann, Hayk Davtyan and Mathew Blurton-Jones
Alzheimer’s disease (AD) is the leading cause of dementia. The two histopathological markers of AD are amyloid plaques composed of the amyloid-β (Aβ) peptide, and neurofibrillary tangles of aggregated, abnorma...
Authors: Maud Gratuze, Cheryl E. G. Leyns and David M. Holtzman
Activation of microglia, the resident immune cells of the central nervous system, is a prominent pathological hallmark of Alzheimer’s disease (AD). However, the gene expression changes underlying microglia act...
Authors: Hong Wang, Yupeng Li, John W. Ryder, Justin T. Hole, Philip J. Ebert, David C. Airey, Hui-Rong Qian, Benjamin Logsdon, Alice Fisher, Zeshan Ahmed, Tracey K. Murray, Annalisa Cavallini, Suchira Bose, Brian J. Eastwood, David A. Collier, Jeffrey L. Dage…
Alzheimer’s Disease (AD), the most prevalent neurodegenerative disease of aging, affects one in eight older Americans. Nearly all drug treatments tested for AD today have failed to show any efficacy. There is ...
Authors: Jiqing Cao, Jianwei Hou, Jing Ping and Dongming Cai
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
