Genetic variants of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) confer increased risk of developing late-onset Alzheimer’s Disease (LOAD) and other neurodegenerative disorders. Recent studies pro...
Authors: Shane M. Bemiller, Tyler J. McCray, Kevin Allan, Shane V. Formica, Guixiang Xu, Gina Wilson, Olga N. Kokiko-Cochran, Samuel D. Crish, Cristian A. Lasagna-Reeves, Richard M. Ransohoff, Gary E. Landreth and Bruce T. Lamb
Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder, affecting millions of people worldwide. Although dysfunction of multiple neurotransmitter systems including cholinergic, glut...
Authors: Yue Wang, Zheng Wu, Yu-Ting Bai, Gang-Yi Wu and Gong Chen
MAPT mutations cause neurodegenerative diseases such as frontotemporal dementia but, strikingly, patients with the same mutation may have different clinical phenotypes.
Authors: Ghazaleh Eskandari-Sedighi, Nathalie Daude, Hristina Gapeshina, David W. Sanders, Razieh Kamali-Jamil, Jing Yang, Beipei Shi, Holger Wille, Bernardino Ghetti, Marc I. Diamond, Christopher Janus and David Westaway
Optic nerve injury is an important pathological component in neurodegenerative diseases such as traumatic optic neuropathies and glaucoma. The molecular signaling pathway(s) critical for retinal ganglion cell ...
Authors: Stephanie B. Syc-Mazurek, Kimberly A. Fernandes, Michael P. Wilson, Peter Shrager and Richard T. Libby
Early onset Parkinson’s disease is caused by variants in PINK1, parkin, and DJ-1. PINK1 and parkin operate in pathways that preserve mitochondrial integrity, but the function of DJ-1 and how it relates to PINK1 a...
Authors: David N. Hauser, Adamantios Mamais, Melissa M. Conti, Christopher T. Primiani, Ravindran Kumaran, Allissa A. Dillman, Rebekah G. Langston, Alexandra Beilina, Joseph H. Garcia, Alberto Diaz-Ruiz, Michel Bernier, Fabienne C. Fiesel, Xu Hou, Wolfdieter Springer, Yan Li, Rafael de Cabo…
There are inconsistences regarding the correlation between diabetes or fasting blood glucose concentrations and the risk and survival of amyotrophic lateral sclerosis (ALS) in the previous studies. Moreover, t...
Authors: Qian-Qian Wei, Yongping Chen, Bei Cao, Ru Wei Ou, Lingyu Zhang, Yanbing Hou, Xiang Gao and Huifang Shang
Retinitis pigmentosa (RP) is the most common inherited retinal degenerative disease yet with no effective treatment available. The sigma-1 receptor (S1R), a ligand-regulated chaperone, emerges as a potential r...
Authors: Huan Yang, Yingmei Fu, Xinying Liu, Pawan K. Shahi, Timur A. Mavlyutov, Jun Li, Annie Yao, Steven Z.-W. Guo, Bikash R. Pattnaik and Lian-Wang Guo
White matter hyperintensities (WMH) are an important biomarker of cumulative vascular brain injury and have been associated with cognitive decline and an increased risk of dementia, stroke, depression, and gai...
Authors: Honghuang Lin, Claudia Satizabal, Zhijun Xie, Qiong Yang, Tianxiao Huan, Roby Joehanes, Chengping Wen, Peter J. Munson, Alexa Beiser, Daniel Levy and Sudha Seshadri
Pharmacologic inhibition of C5aR1, a receptor for the complement activation proinflammatory fragment, C5a, suppressed pathology and cognitive deficits in Alzheimer's disease (AD) mouse models. To validate that...
Authors: Michael X. Hernandez, Shan Jiang, Tracy A. Cole, Shu-Hui Chu, Maria I. Fonseca, Melody J. Fang, Lindsay A. Hohsfield, Maria D. Torres, Kim N. Green, Rick A. Wetsel, Ali Mortazavi and Andrea J. Tenner
Protein inclusions are a predominant molecular pathology found in numerous neurodegenerative diseases, including amyotrophic lateral sclerosis and Huntington’s disease. Protein inclusions form in discrete area...
Authors: Rebecca San Gil, Lezanne Ooi, Justin J. Yerbury and Heath Ecroyd
The molecular mechanism underlying progressive memory loss in Alzheimer’s disease is poorly understood. Neurogenesis in the adult hippocampus is a dynamic process that continuously changes the dentate gyrus an...
Authors: Carolyn Hollands, Matthew Kyle Tobin, Michael Hsu, Kianna Musaraca, Tzong-Shiue Yu, Rachana Mishra, Steven G. Kernie and Orly Lazarov
There is still a substantial unmet need for less invasive and lower-cost blood-based biomarkers to detect brain Alzheimer’s disease (AD) pathology. This study is aimed to determine whether quantification of pl...
Authors: Harutsugu Tatebe, Takashi Kasai, Takuma Ohmichi, Yusuke Kishi, Tomoshi Kakeya, Masaaki Waragai, Masaki Kondo, David Allsop and Takahiko Tokuda
Mutations resulting in progranulin (PGRN) haploinsufficiency cause frontotemporal lobar degeneration with TDP-43-positive inclusions (FTLD-TDP), a devastating neurodegenerative disease. PGRN is localized to th...
Authors: Xiaolai Zhou, Daniel H. Paushter, Tuancheng Feng, Lirong Sun, Thomas Reinheckel and Fenghua Hu
Alzheimer’s disease (AD)-linked β-amyloid (Aβ) accumulates in multivesicular bodies (MVBs) with the onset of AD pathogenesis. Alterations in endosomes are among the earliest changes associated with AD but the ...
Authors: Katarina Willén, James R. Edgar, Takafumi Hasegawa, Nobuyuki Tanaka, Clare E. Futter and Gunnar K. Gouras
Alzheimer’s Disease (AD), characterized by accumulation of beta-amyloid (Aβ) plaques in the brain, can be caused by age-related failures to clear Aβ from the brain through pathways that involve the cerebrovasc...
Authors: Jérôme Robert, Emily B. Button, Sophie Stukas, Guilaine K. Boyce, Ebrima Gibbs, Catherine M. Cowan, Megan Gilmour, Wai Hang Cheng, Sonja K. Soo, Brian Yuen, Arvin Bahrabadi, Kevin Kang, Iva Kulic, Gordon Francis, Neil Cashman and Cheryl L. Wellington
Extracellular Tau is toxic for neighboring cells, and it contributes to the progression of AD. The CX3CL1/CX3CR1 axis is an important neuron/microglia communication mechanism.
Authors: Marta Bolós, María Llorens-Martín, Juan Ramón Perea, Jerónimo Jurado-Arjona, Alberto Rábano, Félix Hernández and Jesús Avila
Tau is an axon-enriched protein that binds to and stabilizes microtubules, and hence plays a crucial role in neuronal function. In Alzheimer’s disease (AD), pathological tau accumulation correlates with cognit...
Authors: Marius Chiasseu, Luis Alarcon-Martinez, Nicolas Belforte, Heberto Quintero, Florence Dotigny, Laurie Destroismaisons, Christine Vande Velde, Fany Panayi, Caroline Louis and Adriana Di Polo
Adverse effects in diabetic mothers offspring (DMO) are a major concern of increasing incidence. Among these, chronic central complications in DMO remain poorly understood, and in extreme cases, diabetes can e...
Authors: Juan Jose Ramos-Rodriguez, Daniel Sanchez-Sotano, Alberto Doblas-Marquez, Carmen Infante-Garcia, Simon Lubian-Lopez and Monica Garcia-Alloza
TREM2 variants have been identified as risk factors for Alzheimer’s disease (AD) and other neurodegenerative diseases (NDDs). Because TREM2 encodes a receptor exclusively expressed on immune cells, identificat...
Authors: Taylor R. Jay, Victoria E. von Saucken and Gary E. Landreth
Haploinsufficiency of GRN, the gene encoding progranulin (PGRN), causes frontotemporal lobar degeneration (FTLD), the second most common cause of early-onset dementia. Receptor-mediated lysosomal targeting has...
Authors: Chris W. Lee, Jeannette N. Stankowski, Jeannie Chew, Casey N. Cook, Ying-Wai Lam, Sandra Almeida, Yari Carlomagno, Kwok-Fai Lau, Mercedes Prudencio, Fen-Biao Gao, Matthew Bogyo, Dennis W. Dickson and Leonard Petrucelli
Autosomal-dominant mutations in the Park8 gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been identified to cause up to 40% of the genetic forms of Parkinson’s disease. However, the function and molecula...
Authors: Alena Salašová, Chika Yokota, David Potěšil, Zbyněk Zdráhal, Vítězslav Bryja and Ernest Arenas
Excessive synaptic loss is thought to be one of the earliest events in Alzheimer’s disease (AD). However, the key mechanisms that maintain plasticity of synapses during adulthood or initiate synapse dysfunctio...
Authors: Anthony Bosson, Adrien Paumier, Sylvie Boisseau, Muriel Jacquier-Sarlin, Alain Buisson and Mireille Albrieux
Alpha-synuclein (α-syn) aggregation represents the pathological hallmark of α-synucleinopathies like Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Toll-like rece...
Authors: Serena Venezia, Violetta Refolo, Alexia Polissidis, Leonidas Stefanis, Gregor K. Wenning and Nadia Stefanova
Given multiple studies of brain microRNA (miRNA) in relation to Alzheimer’s disease (AD) with few consistent results and the heterogeneity of this disease, the objective of this study was to explore their mech...
Authors: Ellis Patrick, Sathyapriya Rajagopal, Hon-Kit Andus Wong, Cristin McCabe, Jishu Xu, Anna Tang, Selina H. Imboywa, Julie A. Schneider, Nathalie Pochet, Anna M. Krichevsky, Lori B. Chibnik, David A. Bennett and Philip L. De Jager
Tauopathies are a broad set of neurodegenerative dementias characterized by aggregation of the tau protein into filamentous inclusions that can be found in neurons and glial cells. Activated microglia, astrocy...
Alzheimer’s Disease (AD) is the most prevalent progressive neurodegenerative disease; to date, no AD therapy has proven effective in delaying or preventing the disease course. In the search for novel therapeut...
Authors: Hunter S. Futch, Cara L. Croft, Van Q. Truong, Eric G. Krause and Todd E. Golde
Presenilins play a major role in the pathogenesis of Alzheimer’s disease, in which the hippocampus is particularly vulnerable. Previous studies of Presenilin function in the synapse, however, focused exclusive...
Authors: Sang Hun Lee, David Lutz, Mohanad Mossalam, Vadim Y. Bolshakov, Michael Frotscher and Jie Shen
Microglia are known as resident immune cells in the brain. β-amyloid (Aβ) plaques in the brain of Alzheimer’s disease (AD) are surrounded by microglia, but whether and how microglia affect the formation and ma...
Authors: Ruohe Zhao, Wanling Hu, Julia Tsai, Wei Li and Wen-Biao Gan
Amyotrophic Lateral Sclerosis (ALS) is a fatal and progressive neurodegenerative disorder with identified genetic causes representing a significant minority of all cases. A GGGGCC hexanucleotide repeat expansi...
Authors: Rustam Esanov, Gabriela Toro Cabrera, Nadja S. Andrade, Tania F. Gendron, Robert H. Brown Jr., Michael Benatar, Claes Wahlestedt, Christian Mueller and Zane Zeier
Parkinson’s disease is a multifactorial neurodegenerative disorder, the aetiology of which remains elusive. The primary clinical feature of progressively impaired motor control is caused by a loss of midbrain ...
Authors: James A. Duce, Bruce X. Wong, Hannah Durham, Jean-Christophe Devedjian, David P. Smith and David Devos
Parkinson’s’ disease (PD) and Multiple System Atrophy (MSA) are progressive brain disorders characterized by intracellular accumulations of α-synuclein and nerve cell loss in specific brain areas. This loss ca...
Authors: Tomasz Brudek, Kristian Winge, Jonas Folke, Søren Christensen, Karina Fog, Bente Pakkenberg and Lars Østergaard Pedersen
Prionoid transmission of α-synuclein (αSyn) aggregates along neuroanatomically connected projections is posited to underlie disease progression in α-synucleinopathies. Here, we specifically wanted to study whe...
Authors: Zachary A. Sorrentino, Mieu M.T. Brooks, Vincent Hudson III, Nicola J. Rutherford, Todd E. Golde, Benoit I. Giasson and Paramita Chakrabarty
Alzheimer’s disease (AD) is a highly heritable complex disease with no current effective prevention or treatment. The majority of drugs developed for AD focus on the amyloid cascade hypothesis, which implicate...
Authors: Anastasia G. Efthymiou and Alison M. Goate
Persistent endoplasmic reticulum (ER) stress is thought to drive the pathology of many chronic disorders due to its potential to elicit aberrant inflammatory signaling and facilitate cell death. In neurodegene...
Authors: Neil T. Sprenkle, Savannah G. Sims, Cristina L. Sánchez and Gordon P. Meares
Hyperexcitability of neuronal networks can lead to excessive release of the excitatory neurotransmitter glutamate, which in turn can cause neuronal damage by overactivating NMDA-type glutamate receptors and re...
Authors: Takashi Miyamoto, Liana Stein, Reuben Thomas, Biljana Djukic, Praveen Taneja, Joseph Knox, Keith Vossel and Lennart Mucke
Hyperphosphorylation of microtubule-associated protein tau is a distinct feature of neurofibrillary tangles (NFTs) that are the hallmark of neurodegenerative tauopathies. O-GlcNAcylation is a lesser known post...
Authors: Nicholas B. Hastings, Xiaohai Wang, Lixin Song, Brent D. Butts, Diane Grotz, Richard Hargreaves, J. Fred Hess, Kwok-Lam Karen Hong, Cathy Ruey-Ruey Huang, Lynn Hyde, Maureen Laverty, Julie Lee, Diane Levitan, Sherry X. Lu, Maureen Maguire, Veeravan Mahadomrongkul…
Herpes simplex virus type 1 strain 129 (H129) has represented a promising anterograde neuronal circuit tracing tool, which complements the existing retrograde tracers. However, the current H129 derived tracers...
Mitochondrial dysfunction has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Functional studies of mitochondrial bioenergetics have focused...
Authors: Hibiki Kawamata, Pablo Peixoto, Csaba Konrad, Gloria Palomo, Kirsten Bredvik, Meri Gerges, Federica Valsecchi, Leonard Petrucelli, John M. Ravits, Anatoly Starkov and Giovanni Manfredi
To assess stages of Alzheimer's disease (AD) pathogenesis and the efficacy of drugs during clinical trials, there has been immense interest in the field to establish baseline cerebrospinal fluid (CSF) concentr...
Authors: Brendan P. Lucey, Anne M. Fagan, David M. Holtzman, John C. Morris and Randall J. Bateman
Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative condition that is characterized by progressive loss of motor neurons and the accumulation of aggregated TAR DNA Binding Protein-43 (TDP-4...
Authors: Peter E. A. Ash, Elizabeth A. Stanford, Ali Al Abdulatif, Alejandra Ramirez-Cardenas, Heather I. Ballance, Samantha Boudeau, Amanda Jeh, James M. Murithi, Yorghos Tripodis, George J. Murphy, David H. Sherr and Benjamin Wolozin
The experience from clinical trials indicates that anti-Aβ immunotherapy could be effective in early/pre-clinical stages of AD, whereas at the late stages promoting the clearing of Aβ alone may be insufficient...
Authors: Michael G. Agadjanyan, Karen Zagorski, Irina Petrushina, Hayk Davtyan, Konstantin Kazarian, Maxim Antonenko, Joy Davis, Charles Bon, Mathew Blurton-Jones, David H. Cribbs and Anahit Ghochikyan
The impairment of histone acetylation is causally linked to the cognitive decline in Alzheimer’s disease (AD). In addition to histone acetyltransferases (HATs) and histone deacetylases (HDACs), inhibitor of ac...
Authors: Gao-Shang Chai, Qiong Feng, Zhi-Hao Wang, Yu Hu, Dong-Sheng Sun, Xiao-Guang Li, Dan Ke, Hong-Lian Li, Gong-Ping Liu and Jian-Zhi Wang
Mutations in PINK1 and PARKIN are the most common causes of recessive early-onset Parkinson’s disease (EOPD). Together, the mitochondrial ubiquitin (Ub) kinase PINK1 and the cytosolic E3 Ub ligase PARKIN direct a...
Authors: Maya Ando, Fabienne C. Fiesel, Roman Hudec, Thomas R. Caulfield, Kotaro Ogaki, Paulina Górka-Skoczylas, Dariusz Koziorowski, Andrzej Friedman, Li Chen, Valina L. Dawson, Ted M. Dawson, Guojun Bu, Owen A. Ross, Zbigniew K. Wszolek and Wolfdieter Springer
Chemokine signalling is required for the homing of leukocytes during retinal inflammation, and is associated with pathogenesis of diseases such as age-related macular degeneration (AMD). Here, we explore the r...
Authors: Riccardo Natoli, Nilisha Fernando, Michele Madigan, Joshua A. Chu-Tan, Krisztina Valter, Jan Provis and Matt Rutar
Microglia mediate amyloid-beta peptide (Aβ)-induced neuroinflammation, which is one of the key events in the pathogenesis of Alzheimer’s disease (AD). Decoy receptor 3 (DcR3)/TNFRSF6B is a pleiotropic immunomo...
Parkin (PARK2) is an E3 ubiquitin ligase that is commonly mutated in Familial Parkinson’s Disease (PD). In cell culture models, Parkin is recruited to acutely depolarised mitochondria by PINK1. PINK1 activates...
Authors: Aitor Martinez, Benoit Lectez, Juanma Ramirez, Oliver Popp, James D. Sutherland, Sylvie Urbé, Gunnar Dittmar, Michael J. Clague and Ugo Mayor
Light exposure triggers movement of certain signaling proteins within the cellular compartments of the highly polarized rod photoreceptor cell. This redistribution of proteins between the inner and outer segme...
Authors: Kasey Rose, Steven T. Walston and Jeannie Chen
Amyloid-β oligomers (oAβ) are thought to mediate neurotoxicity in Alzheimer’s disease (AD), and previous studies in AD transgenic mice suggest that calcium dysregulation may contribute to these pathological ef...
Authors: Michal Arbel-Ornath, Eloise Hudry, Josiah R. Boivin, Tadafumi Hashimoto, Shuko Takeda, Kishore V. Kuchibhotla, Steven Hou, Carli R. Lattarulo, Arianna M. Belcher, Naomi Shakerdge, Pariss B. Trujillo, Alona Muzikansky, Rebecca A. Betensky, Bradley T. Hyman and Brian J. Bacskai
FADD (Fas-associated death domain) adaptor is a crucial protein involved in the induction of cell death but also mediates non-apoptotic actions via a phosphorylated form (p-Ser194-FADD). This study investigate...
Authors: Alfredo Ramos-Miguel, Jesús A. García-Sevilla, Alasdair M. Barr, Thomas A. Bayer, Peter Falkai, Sue E. Leurgans, Julie A. Schneider, David A. Bennett, William G. Honer and M. Julia García-Fuster
The mechanisms behind Aβ-peptide accumulation in non-familial Alzheimer’s disease (AD) remain elusive. Proteins of the tetraspanin family modulate Aβ production by interacting to γ-secretase.
