Articles

A role for α-Synuclein in axon growth and its implications in corticostriatal glutamatergic plasticity in Parkinson’s disease

α-Synuclein (α-Syn) is a protein implicated in the pathogenesis of Parkinson’s disease (PD). α-Syn has been shown to associate with membranes and bind acidic phospholipids. However, the physiological importanc...

Authors: Meir Schechter, Jessica Grigoletto, Suaad Abd-Elhadi, Hava Glickstein, Alexander Friedman, Geidy E. Serrano, Thomas G. Beach and Ronit Sharon

Cerebrovascular amyloid Angiopathy in bioengineered vessels is reduced by high-density lipoprotein particles enriched in Apolipoprotein E

Several lines of evidence suggest that high-density lipoprotein (HDL) reduces Alzheimer’s disease (AD) risk by decreasing vascular beta-amyloid (Aβ) deposition and inflammation, however, the mechanisms by whic...

Authors: Jerome Robert, Emily B. Button, Emma M. Martin, Luke McAlary, Zoe Gidden, Megan Gilmour, Guilaine Boyce, Tara M. Caffrey, Andrew Agbay, Amanda Clark, Judith M. Silverman, Neil R. Cashman and Cheryl L. Wellington

Correction to: Parkinson’s disease-related Leucine-rich repeat kinase 2 modulates nuclear morphology and genomic stability in striatal projection neurons during aging

The original article had mistakenly inverted co-author, Wang Zheng’s name. This has since been corrected.

Authors: Xi Chen, Chengsong Xie, Wotu Tian, Lixin Sun, Wang Zheng, Sarah Hawes, Lisa Chang, Justin Kung, Jinhui Ding, Shengdi Chen, Weidong Le and Huaibin Cai

Premature termination codon readthrough upregulates progranulin expression and improves lysosomal function in preclinical models of GRN deficiency

Frontotemporal lobar degeneration (FTLD) is a devastating and progressive disorder, and a common cause of early onset dementia. Progranulin (PGRN) haploinsufficiency due to autosomal dominant mutations in the ...

Authors: Jonathan Frew, Alireza Baradaran-Heravi, Aruna D. Balgi, Xiujuan Wu, Tyler D. Yan, Steve Arns, Fahimeh S. Shidmoossavee, Jason Tan, James B. Jaquith, Karen R. Jansen-West, Francis C. Lynn, Fen-Biao Gao, Leonard Petrucelli, Howard H. Feldman, Ian R. Mackenzie, Michel Roberge…

PINK1 and Parkin mitochondrial quality control: a source of regional vulnerability in Parkinson’s disease

That certain cell types in the central nervous system are more likely to undergo neurodegeneration in Parkinson’s disease is a widely appreciated but poorly understood phenomenon. Many vulnerable subpopulation...

Authors: Preston Ge, Valina L. Dawson and Ted M. Dawson

Initiation and propagation of α-synuclein aggregation in the nervous system

The two main pathological hallmarks of Parkinson’s disease are loss of dopamine neurons in the substantia nigra pars compacta and proteinaceous amyloid fibrils composed mostly of α-synuclein, called Lewy patho...

Authors: Baraa A. Hijaz and Laura A. Volpicelli-Daley

PARIS induced defects in mitochondrial biogenesis drive dopamine neuron loss under conditions of parkin or PINK1 deficiency

Mutations in PINK1 and parkin cause autosomal recessive Parkinson’s disease (PD). Evidence placing PINK1 and parkin in common pathways regulating multiple aspects of mitochondrial quality control is burgeoning...

Authors: Sheila K. Pirooznia, Changqing Yuan, Mohammed Repon Khan, Senthilkumar S. Karuppagounder, Luan Wang, Yulan Xiong, Sung Ung Kang, Yunjong Lee, Valina L. Dawson and Ted M. Dawson

Utilizing minimally purified secreted rAAV for rapid and cost-effective manipulation of gene expression in the CNS

Recombinant adeno-associated virus (rAAV) is widely used in the neuroscience field to manipulate gene expression in the nervous system. However, a limitation to the use of rAAV vectors is the time and expense ...

Authors: Marshall S. Goodwin, Cara L. Croft, Hunter S. Futch, Daniel Ryu, Carolina Ceballos-Diaz, Xuefei Liu, Giavanna Paterno, Catalina Mejia, Doris Deng, Kimberly Menezes, Laura Londono, Kefren Arjona, Mary Parianos, Van Truong, Eva Rostonics, Amanda Hernandez…

Dipeptide repeat proteins inhibit homology-directed DNA double strand break repair in C9ORF72 ALS/FTD

The C9ORF72 hexanucleotide repeat expansion is the most common known genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two fatal age-related neurodegenerative diseases. Th...

Authors: Nadja S. Andrade, Melina Ramic, Rustam Esanov, Wenjun Liu, Mathew J. Rybin, Gabriel Gaidosh, Abbas Abdallah, Samuel Del’Olio, Tyler C. Huff, Nancy T. Chee, Sadhana Anatha, Tania F. Gendron, Claes Wahlestedt, Yanbin Zhang, Michael Benatar, Christian Mueller…

Parkinson’s disease-related Leucine-rich repeat kinase 2 modulates nuclear morphology and genomic stability in striatal projection neurons during aging

Multiple missense mutations in Leucine-rich repeat kinase 2 (LRRK2) are associated with familial forms of late onset Parkinson’s disease (PD), the most common age-related movement disorder. The dysfunction of ...

Authors: Xi Chen, Chengsong Xie, Wotu Tian, Lixin Sun, Wang Zheng, Sarah Hawes, Lisa Chang, Justin Kung, Jinhui Ding, Shengdi Chen, Weidong Le and Huaibin Cai

Circulating cell-free mitochondrial DNA levels in Parkinson’s disease are influenced by treatment

Several studies have linked circulating cell-free mitochondrial DNA (ccf-mtDNA) to human disease. In particular, reduced ccf-mtDNA levels in the cerebrospinal fluid (CSF) of both Alzheimer’s and Parkinson’s di...

Authors: Hannah Lowes, Angela Pyle, Mauro Santibanez-Koref and Gavin Hudson

Therapeutic approaches targeting Apolipoprotein E function in Alzheimer’s disease

One of the primary genetic risk factors for Alzheimer’s disease (AD) is the presence of the Ɛ4 allele of apolipoprotein E (APOE). APOE is a polymorphic lipoprotein that is a major cholesterol carrier in the br...

Authors: Tosha Williams, David R. Borchelt and Paramita Chakrabarty

Elevated methylation levels, reduced expression levels, and frequent contractions in a clinical cohort of C9orf72 expansion carriers

A repeat expansion in the C9orf72-SMCR8 complex subunit (C9orf72) is the most common genetic cause of two debilitating neurodegenerative diseases: amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (...

Authors: Jazmyne L. Jackson, NiCole A. Finch, Matthew C. Baker, Jennifer M. Kachergus, Mariely DeJesus-Hernandez, Kimberly Pereira, Elizabeth Christopher, Mercedes Prudencio, Michael G. Heckman, E. Aubrey Thompson, Dennis W. Dickson, Jaimin Shah, Björn Oskarsson, Leonard Petrucelli, Rosa Rademakers and Marka van Blitterswijk

A pharmacological chaperone improves memory by reducing Aβ and tau neuropathology in a mouse model with plaques and tangles

The vacuolar protein sorting 35 (VPS35) is a major component of the retromer complex system, an ubiquitous multiprotein assembly responsible for sorting and trafficking protein cargos out of the endosomes. VPS...

Authors: Jian-Guo Li, Jin Chiu, Mercy Ramanjulu, Benjamin E. Blass and Domenico Praticò

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

The original article [1] contains an error in the y-axes of Fig. 8’s sub-figures whereby ‘CSF’ is mistakenly mentioned instead of ‘serum’.

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

Alpha-synuclein-induced mitochondrial dysfunction is mediated via a sirtuin 3-dependent pathway

Misfolding and aggregation of the presynaptic protein alpha-synuclein (αsyn) is a hallmark of Parkinson’s disease (PD) and related synucleinopathies. Although predominantly localized in the cytosol, a body of ...

Authors: Jae-Hyeon Park, Jeremy D. Burgess, Ayman H. Faroqi, Natasha N. DeMeo, Fabienne C. Fiesel, Wolfdieter Springer, Marion Delenclos and Pamela J. McLean

VGF-derived peptide TLQP-21 modulates microglial function through C3aR1 signaling pathways and reduces neuropathology in 5xFAD mice

Multiomic studies by several groups in the NIH Accelerating Medicines Partnership for Alzheimer’s Disease (AMP-AD) identified VGF as a major driver of Alzheimer’s disease (AD), also finding that reduced VGF le...

Authors: Farida El Gaamouch, Mickael Audrain, Wei-Jye Lin, Noam Beckmann, Cheng Jiang, Siddharth Hariharan, Peter S. Heeger, Eric E. Schadt, Sam Gandy, Michelle E. Ehrlich and Stephen R. Salton

Contribution of GABAergic interneurons to amyloid-β plaque pathology in an APP knock-in mouse model

The amyloid-β (Aβ) peptide, the primary constituent of amyloid plaques found in Alzheimer’s disease (AD) brains, is derived from sequential proteolytic processing of the Amyloid Precursor Protein (APP). Howeve...

Authors: Heather C. Rice, Gabriele Marcassa, Iordana Chrysidou, Katrien Horré, Tracy L. Young-Pearse, Ulrike C. Müller, Takashi Saito, Takaomi C. Saido, Robert Vassar, Joris de Wit and Bart De Strooper

Promoting tau secretion and propagation by hyperactive p300/CBP via autophagy-lysosomal pathway in tauopathy

The trans-neuronal propagation of tau has been implicated in the progression of tau-mediated neurodegeneration. There is critical knowledge gap in understanding how tau is released and transmitted, and how tha...

Authors: Xu Chen, Yaqiao Li, Chao Wang, Yinyan Tang, Sue-Ann Mok, Richard M. Tsai, Julio C. Rojas, Anna Karydas, Bruce L. Miller, Adam L. Boxer, Jason E. Gestwicki, Michelle Arkin, Ana Maria Cuervo and Li Gan

Longitudinal and nonlinear relations of dietary and Serum cholesterol in midlife with cognitive decline: results from EMCOA study

Previous studies regarding the cholesterol-cognition relationship in midlife have generated conflicting results. We thus investigated whether dietary and blood cholesterol were associated with cognitive decline.

Authors: Yu An, Xiaona Zhang, Ying Wang, Yushan Wang, Wen Liu, Tao Wang, Zhongsheng Qin and Rong Xiao

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