Articles

Genetic perturbations of disease risk genes in mice capture transcriptomic signatures of late-onset Alzheimer’s disease

New genetic and genomic resources have identified multiple genetic risk factors for late-onset Alzheimer’s disease (LOAD) and characterized this common dementia at the molecular level. Experimental studies in ...

Authors: Ravi S. Pandey, Leah Graham, Asli Uyar, Christoph Preuss, Gareth R. Howell and Gregory W. Carter

LRRK2 Biology from structure to dysfunction: research progresses, but the themes remain the same

Since the discovery of leucine-rich repeat kinase 2 (LRRK2) as a protein that is likely central to the aetiology of Parkinson’s disease, a considerable amount of work has gone into uncovering its basic cellula...

Authors: Daniel C. Berwick, George R. Heaton, Sonia Azeggagh and Kirsten Harvey

BrightFocus Alzheimer’s Fast Track 2019

The 3 day workshop “Alzheimer’s Fast Track” is a unique opportunity for graduate students, postdoctoral fellows, or other early-career scientists, focused on Alzheimer’s disease research, to gain new knowledge...

Authors: Keith W. Whitaker, Frank M. LaFerla, Harry W. M. Steinbusch, Cynthia A. Lemere and Diane E. Bovenkamp

Synergistic effects of APOE and sex on the gut microbiome of young EFAD transgenic mice

Alzheimer’s disease (AD) is a fatal neurodegenerative disease. APOE4 is the greatest genetic risk factor for AD, increasing risk up to 15-fold compared to the common APOE3. Importantly, female (♀) APOE4 carriers ...

Authors: Juan Maldonado Weng, Ishita Parikh, Ankur Naqib, Jason York, Stefan J. Green, Steven Estus and Mary Jo LaDu

Generating microglia from human pluripotent stem cells: novel in vitro models for the study of neurodegeneration

Microglia play an essential role for central nervous system (CNS) development and homeostasis and have been implicated in the onset, progression, and clearance of numerous diseases affecting the CNS. Previous ...

Authors: Anna M. Speicher, Heinz Wiendl, Sven G. Meuth and Matthias Pawlowski

Organotypic brain slice cultures to model neurodegenerative proteinopathies

Organotypic slice cultures of brain or spinal cord have been a longstanding tool in neuroscience research but their utility for understanding Alzheimer’s disease (AD) and other neurodegenerative proteinopathie...

Authors: C. L. Croft, H. S. Futch, B. D. Moore and T. E. Golde

Targeted disruption of dual leucine zipper kinase and leucine zipper kinase promotes neuronal survival in a model of diffuse traumatic brain injury

Traumatic brain injury (TBI) is a major cause of CNS neurodegeneration and has no disease-altering therapies. It is commonly associated with a specific type of biomechanical disruption of the axon called traum...

Authors: Derek S. Welsbie, Nikolaos K. Ziogas, Leyan Xu, Byung-Jin Kim, Yusong Ge, Amit K. Patel, Jiwon Ryu, Mohamed Lehar, Athanasios S. Alexandris, Nicholas Stewart, Donald J. Zack and Vassilis E. Koliatsos

Autophagy protein NRBF2 has reduced expression in Alzheimer’s brains and modulates memory and amyloid-beta homeostasis in mice

Dysfunctional autophagy is implicated in Alzheimer’s Disease (AD) pathogenesis. The alterations in the expression of many autophagy related genes (ATGs) have been reported in AD brains; however, the disparity ...

Authors: Véronik Lachance, Qian Wang, Eric Sweet, Insup Choi, Cui-Zan Cai, Xu-Xu Zhuang, Yuanxi Zhang, Jessica Li Jiang, Robert D. Blitzer, Ozlem Bozdagi-Gunal, Bin Zhang, Jia-Hong Lu and Zhenyu Yue

Wild-type Cu/Zn-superoxide dismutase is misfolded in cerebrospinal fluid of sporadic amyotrophic lateral sclerosis

A subset of familial forms of amyotrophic lateral sclerosis (ALS) are caused by mutations in the gene coding Cu/Zn-superoxide dismutase (SOD1). Mutant SOD1 proteins are susceptible to misfolding and abnormally...

Authors: Eiichi Tokuda, Yo-ichi Takei, Shinji Ohara, Noriko Fujiwara, Isao Hozumi and Yoshiaki Furukawa

Application of CRISPR genetic screens to investigate neurological diseases

The adoption of CRISPR-Cas9 technology for functional genetic screens has been a transformative advance. Due to its modular nature, this technology can be customized to address a myriad of questions. To date, ...

Authors: Raphaella W. L. So, Sai Wai Chung, Heather H. C. Lau, Jeremy J. Watts, Erin Gaudette, Zaid A. M. Al-Azzawi, Jossana Bishay, Lilian Tsai-Wei Lin, Julia Joung, Xinzhu Wang and Gerold Schmitt-Ulms

Reduced sphingolipid hydrolase activities, substrate accumulation and ganglioside decline in Parkinson’s disease

Haploinsufficiency in the Gaucher disease GBA gene, which encodes the lysosomal glucocerebrosidase GBA, and ageing represent major risk factors for developing Parkinson’s disease (PD). Recently, more than fifty o...

Authors: Mylene Huebecker, Elizabeth B. Moloney, Aarnoud C. van der Spoel, David A. Priestman, Ole Isacson, Penelope J. Hallett and Frances M. Platt

Neurofilament light chain is a promising serum biomarker in spinocerebellar ataxia type 3

Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of autosomal dominantly inherited spinocerebellar ataxias (SCAs). No validated blood biomarker is available to assess either disease progression ...

Authors: Quan-Fu Li, Yi Dong, Lu Yang, Juan-Juan Xie, Yin Ma, Yi-Chu Du, Hao-Ling Cheng, Wang Ni and Zhi-Ying Wu

Targeting tauopathy with engineered tau-degrading intrabodies

The accumulation of pathological tau is the main component of neurofibrillary tangles and other tau aggregates in several neurodegenerative diseases, referred to as tauopathies. Recently, immunotherapeutic app...

Authors: Gilbert Gallardo, Connie H. Wong, Sara M. Ricardez, Carolyn N. Mann, Kent H. Lin, Cheryl E. G. Leyns, Hong Jiang and David M. Holtzman

Lack of hepatic apoE does not influence early Aβ deposition: observations from a new APOE knock-in model

The apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset Alzheimer disease (AD). ApoE is produced by both astrocytes and microglia in the brain, whereas hepatocytes produce the majorit...

Authors: Tien-Phat V. Huynh, Chao Wang, Ainsley C. Tran, G. Travis Tabor, Thomas E. Mahan, Caroline M. Francis, Mary Beth Finn, Rebecca Spellman, Melissa Manis, Rudolph E. Tanzi, Jason D. Ulrich and David M. Holtzman

Glucocerebrosidase and its relevance to Parkinson disease

Mutations in GBA1, the gene encoding the lysosomal enzyme glucocerebrosidase, are among the most common known genetic risk factors for the development of Parkinson disease and related synucleinopathies. A great d...

Authors: Jenny Do, Cindy McKinney, Pankaj Sharma and Ellen Sidransky

Impaired dopamine metabolism in Parkinson’s disease pathogenesis

A full understanding of Parkinson’s Disease etiopathogenesis and of the causes of the preferential vulnerability of nigrostriatal dopaminergic neurons is still an unsolved puzzle. A multiple-hit hypothesis has...

Authors: Anna Masato, Nicoletta Plotegher, Daniela Boassa and Luigi Bubacco

Microglia affect α-synuclein cell-to-cell transfer in a mouse model of Parkinson’s disease

Cell-to-cell propagation of α-synuclein (α-syn) aggregates is thought to contribute to the pathogenesis of Parkinson’s disease (PD) and underlie the spread of α-syn neuropathology. Increased pro-inflammatory c...

Authors: Sonia George, Nolwen L. Rey, Trevor Tyson, Corinne Esquibel, Lindsay Meyerdirk, Emily Schulz, Steven Pierce, Amanda R. Burmeister, Zachary Madaj, Jennifer A. Steiner, Martha L. Escobar Galvis, Lena Brundin and Patrik Brundin

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…