Article
Clinical Neurology
Marina Picillo, Giulio Salerno, Maria Francesca Tepedino, Filomena Abate, Sofia Cuoco, Marco Gioia, Alessia Coppola, Roberto Erro, Maria Teresa Pellecchia, Nicola Rosa, Paolo Barone, Maddalena De Bernardo
Summary: This study describes retinal layer thickness in patients with progressive supranuclear palsy (PSP) compared to healthy controls using spectral-domain optical coherence tomography (SD-OCT). The results show significant thinning of certain retinal layers in PSP patients compared to controls. The study also finds a significant correlation between retinal layer thickness and visuospatial abilities.
NEUROLOGICAL SCIENCES
(2022)
Article
Medicine, General & Internal
Maddalena De Bernardo, Francesco Diana, Marco Gioia, Martina De Luca, Maria Francesca Tepedino, Maria Teresa Pellecchia, Nicola Rosa, Paolo Barone, Marina Picillo
Summary: This study explored the potential differences in choroidal structure between PSP patients and healthy controls. It found that retinal thicknesses were significantly correlated with cerebral white matter changes. However, no significant differences were found in choroidal evaluation between the two groups.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Clinical Neurology
Nils Briel, Viktoria C. Ruf, Katrin Pratsch, Sigrun Roeber, Jeannine Widmann, Janina Mielke, Mario M. Dorostkar, Otto Windl, Thomas Arzberger, Jochen Herms, Felix L. Struebing
Summary: This study used chromatin data from single nuclei to identify disease-related molecular changes associated with astrocytes in the brains of CBD and PSP patients, revealing insights into the regulatory mechanisms of disease development. The research findings expand our knowledge on risk gene involvement (such as MAPT, MAPK8, and NFE2L2) and molecular pathways leading to phenotypic changes in CBD and PSP.
ACTA NEUROPATHOLOGICA
(2022)
Letter
Clinical Neurology
Chelsey ShengQi Zhao, Lei Yan, Wenqing He, Lee Cyn Ang, Qi Zhang
Summary: Neuropathological diagnosis of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) involves interpreting tau morphology through extensive brain sampling. Subcortical tau burden can effectively differentiate between PSP and CBD, with the tau pallido-claustral ratio showing promise as a diagnostic indicator for these conditions.
Review
Immunology
Nastaran Karimi, Feyza Bayram Catak, Ebru Arslan, Amene Saghazadeh, Nima Rezaei
Summary: Tau, a protein associated with more than 25 neurological disorders, has been the target of research for finding novel therapeutic agents. This article reviews the latest animal and clinical studies on tau-based immunotherapies and drugs for Alzheimer's disease and progressive supranuclear palsy.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Clinical Neurology
M. -Marsel Mesulam, Christina A. Coventry, Eileen H. Bigio, Jaiashre Sridhar, Nathan Gill, Angela J. Fought, Hui Zhang, Cynthia K. Thompson, Changiz Geula, Tamar Gefen, Margaret Flanagan, Qinwen Mao, Sandra Weintraub, Emily J. Rogalski
Summary: Primary progressive aphasia is a neurodegenerative disease that selectively impairs language function. Autopsies and longitudinal studies have shown that primary progressive aphasia has various neuropathological changes, with Alzheimer's disease being the most common. Different variants of primary progressive aphasia have distinct neuropathological correlates, and word comprehension impairments are strong predictors of underlying neuropathology. Different types of primary progressive aphasia have different patterns of cortical atrophy, but all show severe damage to the left hemisphere language network. This study is important for understanding the neuropathological and clinical differences in primary progressive aphasia.
Article
Clinical Neurology
Nils Briel, Katrin Pratsch, Sigrun Roeber, Thomas Arzberger, Jochen Herms
Summary: Research suggests that pTau in astrocytes plays an important role in maintaining synaptic integrity in Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD), and may be associated with cognitive dysfunction in CBD.
Review
Clinical Neurology
Shane Lyons, Dominic Trepel, Tim Lynch, Richard Walsh, Sean O'Dowd
Summary: This study conducted a systematic review to investigate the incidence and prevalence of progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). The findings showed heterogeneity in the epidemiology of these conditions, highlighting the need for further research to understand their true burden.
JOURNAL OF NEUROLOGY
(2023)
Review
Clinical Neurology
Ariane Veilleux Carpentier, Nikolaus R. McFarland
Summary: This review discusses the clinical presentation and treatment of progressive supranuclear palsy (PSP), and focuses on the application and limitations of the 2017 Movement Disorders Society PSP criteria. There is significant overlap between different variants of PSP and the severity and predominant symptoms of the disease evolve over time. The differential diagnosis of PSP is continuously evolving and includes other tauopathies, neurodegenerative, genetic, autoimmune, and infectious disorders. Guidelines for clinical management of PSP patients have recently been published.
CURRENT OPINION IN NEUROLOGY
(2023)
Article
Clinical Neurology
Kyung Ah Woo, Joo Young Shin, Heejung Kim, Jeeyun Ahn, Beomseok Jeon, Jee-Young Lee
Summary: PSP patients showed global pRNFL thinning compared to controls, which correlated with disease severity. Nasal pRNFL thinning was positively correlated with disease progression, while global pRNFL thickness showed potential associations with nonmotor items in the PSP rating scale.
JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Morgane Darricau, Taxiarchis Katsinelos, Flavio Raschella, Tomislav Milekovic, Louis Crochemore, Qin Li, Gregoire Courtine, William A. McEwan, Benjamin Dehay, Erwan Bezard, Vincent Planche
Summary: This study demonstrates that progressive supranuclear palsy (PSP) patient-derived tau aggregates can induce motor and behavioral impairments in non-human primates, showing characteristics of prion-like seeding and spreading of PSP lesions. This pilot study paves the way for using PSP tau-injected macaques as a relevant animal model to accelerate drug development for this rare and fatal neurodegenerative disease.
Article
Pharmacology & Pharmacy
David G. Coughlin, Irene Litvan
Summary: This article reviews the clinicopathological correlates and biomarkers of PSP and the progress of disease-modulating therapies for PSP. Experts believe that various factors, including patient selection, treatment timing, lack of biomarkers for prodromal diagnosis, and brain penetration of therapies, have hindered the success of tau-directed therapies in PSP. Coupled with early intervention, targeting upstream factors of tau accumulation and cell death may be necessary to modulate the disease course.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2022)
Article
Clinical Neurology
Yuichi Riku, Yasushi Iwasaki, Shinsuke Ishigaki, Akio Akagi, Masato Hasegawa, Kenya Nishioka, Yuanzhe Li, Miho Riku, Takeshi Ikeuchi, Yusuke Fujioka, Hiroaki Miyahara, Jun Sone, Nobutaka Hattori, Mari Yoshida, Masahisa Katsuno, Gen Sobue
Summary: Mislocalization and cytoplasmic aggregation of TDP-43 in spinal cord motor neurons have been found in various neurological disorders, suggesting mechanistic links. Additionally, the severity of TDP-43 pathology in the spinal cord correlates with the severity of 4R-tau aggregates. These findings provide insights into the pathology and potential mechanisms underlying TDP-43-related diseases.
Review
Neurosciences
Nathalie Bendstrup, Anne-Mette Hejl, Lisette Salvesen
Summary: This systematic review evaluated the utility of neurofilament light in cerebrospinal fluid (CSF) for differentiating frontotemporal dementia (FTD) from progressive supranuclear palsy (PSP). The majority of studies included in this review found a higher level of neurofilament light in CSF in patients with FTD compared to patients with PSP; however, the results were inconsistent, indicating a need for further prospective studies.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Konstantin Messerschmidt, Henryk Barthel, Matthias Brendel, Cordula Scherlach, Karl-Titus Hoffmann, Boris-Stephan Rauchmann, Michael Rullmann, Kenneth Marek, Victor L. Villemagne, Jost-Julian Rumpf, Dorothee Saur, Matthias L. Schroeter, Andreas Schildan, Marianne Patt, Leonie Beyer, Mengmeng Song, Carla Palleis, Sabrina Katzdobler, Urban M. Fietzek, Gesine Respondek, Maximilian Scheifele, Alexander Nitschmann, Christian Zach, Olivier Barret, Jennifer Madonia, David Russell, Andrew W. Stephens, Norman Koglin, Sigrun Roeber, Jochen Herms, Kai Boetzel, Peter Bartenstein, Johannes Levin, John P. Seibyl, Guenter Hoeglinger, Joseph Classen, Osama Sabri
Summary: This study investigates the potential of F-18-PI-2620 tau PET in improving the imaging diagnosis of PSP. The results show that adding F-18-PI-2620 tau PET to structural MRI can improve the accuracy of PSP imaging diagnosis, especially in early stages of the disease.
JOURNAL OF NUCLEAR MEDICINE
(2022)
Editorial Material
Clinical Neurology
David Irwin
Summary: Therapeutic development for familial forms of FTLD is rapidly growing, and there is a need for adequate clinical tools to measure treatment effect, as addressed by Peakman et al.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Article
Clinical Neurology
Whitley W. Aamodt, Teresa Waligorska, Junchao Shen, Thomas F. Tropea, Andrew Siderowf, Daniel Weintraub, Murray Grossman, David Irwin, David A. Wolk, Sharon X. Xie, John Q. Trojanowski, Leslie M. Shaw, Alice S. Chen-Plotkin
Summary: The study found that neurofilament light chain protein (NfL) is associated with cognitive function in Parkinson's disease (PD) patients and can predict future cognitive decline. Plasma NfL was identified as a useful prognostic biomarker for PD, predicting the likelihood of PD patients converting to mild cognitive impairment or dementia.
MOVEMENT DISORDERS
(2021)
Article
Clinical Neurology
Sandhitsu R. Das, Xueying Lyu, Michael Tran Duong, Long Xie, Lauren McCollum, Robin Flores, Michael DiCalogero, David J. Irwin, Bradford C. Dickerson, Ilya M. Nasrallah, Paul A. Yushkevich, David A. Wolk
Summary: The study aimed to investigate the impact of Tau neurofibrillary tangles on neurodegeneration, and identified age and burden of white matter hyperintensity lesions as related modulatory factors. Data analysis showed that grouping individuals based on the relationship between Tau neurofibrillary tangles and neurodegeneration may help identify potential contributors to neurodegeneration.
ANNALS OF NEUROLOGY
(2021)
Article
Biochemical Research Methods
Jian Hu, Xiangjie Li, Kyle Coleman, Amelia Schroeder, Nan Ma, David J. Irwin, Edward B. Lee, Russell T. Shinohara, Mingyao Li
Summary: SpaGCN is a spatially resolved transcriptomics data analysis tool that uses graph convolutional networks to identify spatial domains and spatially variable genes. By integrating gene expression, spatial location, and histology, SpaGCN can detect genes with enriched spatial expression patterns and transferable to other datasets for studying spatial gene expression variation. SpaGCN is computationally fast, platform independent, and ideal for diverse SRT studies.
Article
Clinical Neurology
Thomas F. Tropea, Teresa Waligorska, Sharon X. Xie, Ilya M. Nasrallah, Katheryn A. Q. Cousins, John Q. Trojanowski, Murray Grossman, David J. Irwin, Daniel Weintraub, Edward B. Lee, David A. Wolk, Alice S. Chen-Plotkin, Leslie M. Shaw
Summary: The objective of this study was to determine if plasma tau phosphorylated at threonine 181 (p-tau181) can distinguish Alzheimer's disease (AD) from normal cognition (NC) in adults, predict cognitive and functional decline, and validate findings in an external cohort. The results showed that plasma p-tau181 can accurately differentiate AD pathology from NC, and higher levels of p-tau181 are associated with faster cognitive and functional decline.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Letter
Clinical Neurology
Thomas F. Tropea, Isabela Albuja, Katheryn A. Q. Cousins, David J. Irwin, Edward B. Lee, Alice S. Chen-Plotkin
ANNALS OF NEUROLOGY
(2023)
Article
Clinical Neurology
Alexandra L. Young, Jacob W. Vogel, John L. Robinson, Corey T. McMillan, Rik Ossenkoppele, David A. Wolk, David J. Irwin, Lauren Elman, Murray Grossman, Virginia M. Y. Lee, Edward B. Lee, Oskar Hansson
Summary: Through data-driven disease progression modelling, a fine-grained empirical staging system for TAR DNA-binding protein-43 (TDP-43) proteinopathies has been established, which can accurately classify frontotemporal lobar degeneration due to TDP-43 (FTLD-TDP), amyotrophic lateral sclerosis (ALS) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). The study reveals substantial heterogeneity in the progression patterns of ALS and FTLD-TDP, and highlights the need for further investigation in larger cross-cohort studies.
Article
Clinical Neurology
John L. Robinson, Sharon X. Xie, Daniel R. Baer, EunRan Suh, Vivianna M. Van Deerlin, Nicholas J. Loh, David J. Irwin, Corey T. McMillan, David A. Wolk, Alice Chen-Plotkin, Daniel Weintraub, Theresa Schuck, Virginia M. Y. Lee, John Q. Trojanowski, Edward B. Lee
Summary: In this retrospective study, the incidence of 10 pathologies in neurodegenerative disease (ND) and normal aging was examined, with up to seven pathologies observed concurrently resulting in 161 different combinations. The presence of multiple additive pathologies was associated with factors such as longer disease duration, clinical dementia, older age, and APOE e4 status.
Review
Clinical Neurology
David G. Coughlin, David J. Irwin
Summary: Several advances have been made in fluid and tissue-based biomarkers for Parkinson's disease (PD) and other synucleinopathies in the last few years. Immunohistochemistry, immunofluorescence, and alpha-synuclein seeding amplification assays now offer a crucial advancement in identifying different species of alpha-synuclein in PD patients. Co-pathology of Alzheimer's disease (AD) is commonly found in PD and dementia with Lewy bodies (DLB), and biofluid biomarkers for tau and amyloid beta species can detect this co-pathology.
Article
Clinical Neurology
Katheryn A. Q. Cousins, David J. Irwin, Alice Chen-Plotkin, Leslie M. Shaw, Sanaz Arezoumandan, Edward B. Lee, David A. Wolk, Daniel Weintraub, Meredith Spindler, Andres Deik, Murray Grossman, Thomas F. Tropea
Summary: This study found that plasma GFAP may be sensitive to concomitant AD pathology in LBSD, especially accumulation of beta-amyloid plaques.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Review
Medical Laboratory Technology
Ju Hee Kang, Magdalena Korecka, Edward B. Lee, Katheryn A. Q. Cousins, Thomas F. Tropea, Alice A. Chen-Plotkin, David J. Irwin, David Wolk, Magdalena Brylska, Yang Wan, Leslie M. Shaw
Summary: Development of validated biomarkers for early detection of Alzheimer's disease neuropathology is crucial for therapeutic trials. Although CSF and neuroimaging biomarkers have limitations, there is a growing focus on accelerating the development of blood-based AD biomarkers. The use of the AT(N) classification by CSF and imaging biomarkers provides a more objective diagnosis of AD. Blood-based AD biomarkers can be utilized as screening tools in therapeutic trials and clinical care.
CLINICAL CHEMISTRY
(2023)
Article
Clinical Neurology
Min Chen, Sarah Burke, Christopher A. Olm, David J. Irwin, Lauren Massimo, Edward B. Lee, John Q. Trojanowski, James C. Gee, Murray Grossman
Summary: Chen et al. used graph-theoretic analyses of antemortem, multimodal MRIs to examine spreading pathology in structural networks of those with autopsy-confirmed frontotemporal lobar degeneration with either tau or transactional DNA binding protein of similar to 43 kDa inclusions. They report distinct patterns of long-range and short-range network degradation between the two pathologies, suggesting different mechanisms for their spread.
BRAIN COMMUNICATIONS
(2023)
Article
Clinical Neurology
Sanjana Shellikeri, Sunghye Cho, Sharon Ash, Carmen Gonzalez-Recober, Corey T. Mcmillan, Lauren Elman, Colin Quinn, Defne A. Amado, Michael Baer, David J. Irwin, Lauren Massimo, Christopher A. Olm, Mark Y. Liberman, Murray Grossman, Naomi Nevler
Summary: This study evaluated the effectiveness of automated digital speech measures in assessing bulbar motor impairments in patients with ALS-FTD spectrum disorders. The results showed that vowel measures derived from spontaneous speech were able to effectively assess bulbar dysfunction, with greater sensitivity and specificity compared to traditional assessments such as speaking rate.
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
(2023)
Article
Cell Biology
Marta del Campo, Carel F. W. Peeters, Erik C. B. Johnson, Lisa Vermunt, Yanaika S. Hok-A-Hin, Mirrelijn van Nee, Alice Chen-Plotkin, David J. Irwin, William T. Hu, James J. Lah, Nicholas T. Seyfried, Eric B. Dammer, Gonzalo Herradon, Lieke H. Meeter, John van Swieten, Daniel Alcolea, Alberto Lleo, Allan I. Levey, Afina W. Lemstra, Yolande A. L. Pijnenburg, Pieter J. Visser, Betty M. Tijms, Wiesje M. van der Flier, Charlotte E. Teunissen
Summary: This study identifies specific dysregulated CSF proteins along the AD continuum, reflecting the multifactorial nature of disease progression. Some of these dysregulated proteins can be used as biomarkers for the diagnosis and clinical trials of AD.
Article
Clinical Neurology
David G. Coughlin, H. Branch Coslett, Claire Peterson, Jeffrey S. Phillips, Corey McMillan, Edward B. Lee, John Q. Trojanowski, Murray Grossman, David J. Irwin
Summary: This study reported a case with overlapping clinical features of synucleinopathy and tauopathy, and through biomarker characterization and post-mortem sampling, showed lateralized tau and alpha-synuclein pathology suggesting possible synergistic relationships.
ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS
(2022)