Articles

A circuit view of deep brain stimulation in Alzheimer’s disease and the possible mechanisms

Alzheimer’s disease (AD) is characterized by chronic progressive cognitive deterioration frequently accompanied by psychopathological symptoms, including changes in personality and social isolation, which seve...

Authors: Danfang Yu, Huanhuan Yan, Jun Zhou, Xiaodan Yang, Youming Lu and Yunyun Han

The 5th International Conference on Molecular Neurodegeneration: Overlapping Pathologies and Common Mechanisms

Authors:

The neuropathological diagnosis of Alzheimer’s disease

Alzheimer’s disease is a progressive neurodegenerative disease most often associated with memory deficits and cognitive decline, although less common clinical presentations are increasingly recognized. The car...

Authors: Michael A. DeTure and Dennis W. Dickson

Correction to: Inoculation of α-synuclein preformed fibrils into the mouse gastrointestinal tract induces Lewy body-like aggregates in the brainstem via the vagus nerve

The original article [1] mistakenly omitted essential information regarding Fig. 1c; thus, the authors would like to note that Fig. 1c describes transmission electron microscopy of α-Syn PFFs before sonication.

Authors: Norihito Uemura, Hisashi Yagi, Maiko T. Uemura, Yusuke Hatanaka, Hodaka Yamakado and Ryosuke Takahashi

Alpha-synuclein structure and Parkinson’s disease – lessons and emerging principles

Alpha-synuclein (αS) is the major constituent of Lewy bodies and a pathogenic hallmark of all synucleinopathathies, including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atro...

Authors: Richard M. Meade, David P. Fairlie and Jody M. Mason

Pineal gland dysfunction in Alzheimer’s disease: relationship with the immune-pineal axis, sleep disturbance, and neurogenesis

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 ...

Authors: Juhyun Song

Dynactin1 depletion leads to neuromuscular synapse instability and functional abnormalities

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

Synaptic and memory dysfunction induced by tau oligomers is rescued by up-regulation of the nitric oxide cascade

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

Hippocampal stem cells promotes synaptic resistance to the dysfunctional impact of amyloid beta oligomers via secreted exosomes

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 E4, inhibitory network dysfunction, and Alzheimer’s disease

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

α-synuclein in the pathophysiology of Alzheimer’s disease

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...

Authors: Daniel Twohig and Henrietta M. Nielsen

Neuronally derived extracellular vesicles: an emerging tool for understanding Alzheimer’s disease

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

Neuroimaging Biomarkers for Alzheimer’s Disease

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...

Authors: Freddie Márquez and Michael A. Yassa

Endo-lysosomal dysregulations and late-onset Alzheimer’s disease: impact of genetic risk factors

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

The role of neurofilament aggregation in neurodegeneration: lessons from rare inherited neurological disorders

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...

Authors: Alessandro Didonna and Puneet Opal

TREM2 brain transcript-specific studies in AD and TREM2 mutation carriers

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

A CRISPR monkey model unravels a unique function of PINK1 in primate brains

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...

Authors: Weili Yang, Shihua Li and Xiao-Jiang Li

Differential effects of diet- and genetically-induced brain insulin resistance on amyloid pathology in a mouse model of Alzheimer’s disease

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...

Authors: Tomoko Wakabayashi, Kazuki Yamaguchi, Kentaro Matsui, Toshiharu Sano, Tetsuya Kubota, Tadafumi Hashimoto, Ayako Mano, Kaoru Yamada, Yuko Matsuo, Naoto Kubota, Takashi Kadowaki and Takeshi Iwatsubo

Glial phagocytic clearance in Parkinson’s disease

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

Network approach identifies Pacer as an autophagy protein involved in ALS pathogenesis

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…

Functional networks are impaired by elevated tau-protein but reversible in a regulatable Alzheimer’s disease mouse model

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

Human Interleukin-34 facilitates microglia-like cell differentiation and persistent HIV-1 infection in humanized mice

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

Dural lymphatics regulate clearance of extracellular tau from the CNS

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

Sleep oscillation-specific associations with Alzheimer’s disease CSF biomarkers: novel roles for sleep spindles and tau

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…

Aberrant deposition of stress granule-resident proteins linked to C9orf72-associated TDP-43 proteinopathy

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

Differences in neurotropism and neurotoxicity among retrograde viral tracers

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

Reduced presynaptic vesicle stores mediate cellular and network plasticity defects in an early-stage mouse model of Alzheimer’s disease

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

Inhibition of monocyte-like cell extravasation protects from neurodegeneration in DBA/2J glaucoma

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: an update and outlook

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

Emerging new roles of the lysosome and neuronal ceroid lipofuscinoses

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

Recent advances and perspectives of metabolomics-based investigations in Parkinson’s disease

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...

Authors: Yaping Shao and Weidong Le

Glucose transporter 1 critically controls microglial activation through facilitating glycolysis

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

Early increase of CSF sTREM2 in Alzheimer’s disease is associated with tau related-neurodegeneration but not with amyloid-β pathology

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…

Proteolytic cleavage of Beclin 1 exacerbates neurodegeneration

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

Development and validation of a simplified method to generate human microglia from pluripotent stem cells

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

New insights into the role of TREM2 in Alzheimer’s disease

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

Genome-wide RNAseq study of the molecular mechanisms underlying microglia activation in response to pathological tau perturbation in the rTg4510 tau transgenic animal model

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…

Advances in developing novel therapeutic strategies for Alzheimer’s disease

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

Disease-modifying effects of metabolic perturbations in ALS/FTLD

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

GSK3β-mediated tau hyperphosphorylation triggers diabetic retinal neurodegeneration by disrupting synaptic and mitochondrial functions

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...

Authors: Huazhang Zhu, Weizhen Zhang, Yingying Zhao, Xingsheng Shu, Wencong Wang, Dandan Wang, Yangfan Yang, Zhijun He, Xiaomei Wang and Ying Ying

Functional alterations of myeloid cells during the course of Alzheimer’s disease

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

Tissue-enhanced plasma proteomic analysis for disease stratification in amyotrophic lateral sclerosis

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

A brain-penetrant triazolopyrimidine enhances microtubule-stability, reduces axonal dysfunction and decreases tau pathology in a mouse tauopathy model

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

Correction to: Peripheral immune system in aging and Alzheimer’s disease

The original article [1] contained several small omissions and errata contained in Tables 2 and 3; these errors have now been corrected.

Authors: Wei Cao and Hui Zheng

Blood-brain barrier-associated pericytes internalize and clear aggregated amyloid-β42 by LRP1-dependent apolipoprotein E isoform-specific mechanism

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

Essential roles of mitochondrial biogenesis regulator Nrf1 in retinal development and homeostasis

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

Progranulin reduces insoluble TDP-43 levels, slows down axonal degeneration and prolongs survival in mutant TDP-43 mice

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

Deregulation of neuronal miRNAs induced by amyloid-β or TAU pathology

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

ABI3 and PLCG2 missense variants as risk factors for neurodegenerative diseases in Caucasians and African Americans

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…

Deep proteomic network analysis of Alzheimer’s disease brain reveals alterations in RNA binding proteins and RNA splicing associated with disease

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