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Front Aging Neurosci 2020 16;12:126. Epub 2020 Jun 16.

Department of Experimental Medicine and Surgery, Faculty of Medicine and Surgery, University Tor Vergata, Rome, Italy.

Academic centers utilize sequential clinical and neuroimaging assessments, including morphometric ratios, to obtain an unequivocal diagnosis of the non-synucleinopathic forms of Parkinsonism, such as progressive supranuclear palsy (PSP), however, a 1-2 year follow-up is required. The on-going long-lasting trials using anti-tau antibodies for PSP patients might therefore be biased by the incorrect enrollment of Parkinson's disease (PD) patients manifesting early axial signs. This perspective study aimed at achieving two major goals: first, to summarize the established biomarker candidates found in cerebrospinal fluid (CSF) in probable PSP patients, including low p-tau and altered neurofilaments. Read More

Brain Sci 2020 Jun 23;10(6). Epub 2020 Jun 23.

Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.

Atypical Parkinsonian syndromes with prominent frontal lobe involvement can occur in the 4R-taupathies progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Secondary forms of movement disorders may occur in the context of autoimmune encephalitis with antineuronal antibodies, such as anti-glycine receptor (anti-GlyR) antibodies, which are typically associated with Stiff-Person spectrum syndrome, or progressive encephalomyelitis with rigidity and myoclonus. Overlaps between neurodegenerative and immunological mechanisms have been recently suggested in anti-IgLON5 disease. Read More

Cell Rep 2020 Jun;31(12):107807

Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute of Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address:

Data-driven analyses are increasingly valued in modern medicine. We integrate quantitative proteomics and transcriptomics from over 1,000 post-mortem brains from six cohorts representing Alzheimer's disease (AD), asymptomatic AD, progressive supranuclear palsy (PSP), and control patients from the Accelerating Medicines Partnership - Alzheimer's Disease consortium. We define robust co-expression trajectories related to disease progression, including early neuronal, microglial, astrocyte, and immune response modules, and later mRNA splicing and mitochondrial modules. Read More

Acta Neuropathol Commun 2020 Jun 22;8(1):88. Epub 2020 Jun 22.

Department of Neuroscience, College of Medicine, University of Florida, 1275 Center Drive, Gainesville, Florida, 32610, USA.

Tau protein abnormally aggregates in tauopathies, a diverse group of neurologic diseases that includes Alzheimer's disease (AD). In early stages of disease, tau becomes hyperphosphorylated and mislocalized, which can contribute to its aggregation and toxicity. We demonstrate that tau phosphorylation at Ser208 (pSer208) promotes microtubule dysfunction and tau aggregation in cultured cells. Read More

Front Neurol 2020 29;11:446. Epub 2020 May 29.

Memory and Aging Center, University of California, San Francisco, San Francisco, CA, United States.

During early stages, patients with neurodegenerative diseases (NDG) often present with depressive symptoms. However, because depression is a heterogeneous disorder, more precise delineation of the specific depressive symptom profiles that arise early in distinct NDG syndromes is necessary to enhance patient diagnosis and care. Five-hundred and sixty four participants self-reported their depressive symptoms using the Geriatric Depression Scale (GDS), including 111 healthy older control subjects (NC) and 453 patients diagnosed with one of six NDGs who were at the mild stage of disease (CDR® Dementia Staging Instrument ≤ 1) [186 Alzheimer's disease (AD), 76 behavioral variant frontotemporal dementia (bvFTD), 52 semantic variant primary progressive aphasia (svPPA), 46 non-fluent variant PPA (nfvPPA), 49 progressive supranuclear palsy syndrome (PSPS), 44 corticobasal syndrome (CBS)]. Read More

Front Neurosci 2020 28;14:477. Epub 2020 May 28.

Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neuroscience, Bangalore, India.

Purpose: The study is conducted to identify the best corpus callosum (CC) sub-region that corresponds to highest callosal tissue alteration occurred due to Parkinsonism. In this regard the efficacy of local binary pattern (LBP) based texture analysis (TA) of CC is performed to quantify the changes in topographical distribution of callosal fiber connected to different regions of cortex. The extent of highest texture alteration in CC is used for differential diagnosis. Read More

Parkinsonism Relat Disord 2020 May 13;74:67-73. Epub 2020 Mar 13.

Parkinson's Disease & Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Parkinson's Disease and Other Degenerative Movement Disorders Team, European Reference Network for Rare Neurological Diseases (ERN-RND), IDIBAPS, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED:CB06/05/0018-ISCIII), Institut Clínic de Neurociències (Maria de Maeztu Center), Universitat de Barcelona, Barcelona, Catalonia, Spain. Electronic address:

Background: Improved knowledge of the prediagnostic phase of progressive supranuclear palsy (PSP) might provide information on when and how the disease starts, along with the opportunity to test therapies in disease stages with lesser neurodegeneration.

Objective: To explore the symptoms in years preceding the PSP diagnosis.

Methods: This is a single-center retrospective case-control study based on clinical charts review and a structured interview to PSP patients and their caregivers. Read More

Neurobiol Aging 2020 Apr 30. Epub 2020 Apr 30.

Department of Neurology and Alzheimer Center, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. Electronic address:

The aim of this study was to explore whether variants in LRP10, recently associated with Parkinson's disease and dementia with Lewy bodies, are observed in 2 large cohorts (discovery and validation cohort) of patients with progressive supranuclear palsy (PSP). A total of 950 patients with PSP were enrolled: 246 patients with PSP (n = 85 possible (35%), n = 128 probable (52%), n = 33 definite (13%)) in the discovery cohort and 704 patients with definite PSP in the validation cohort. Sanger sequencing of all LRP10 exons and exon-intron boundaries was performed in the discovery cohort, and whole-exome sequencing was performed in the validation cohort. Read More

Eur J Neurol 2020 Jun 11. Epub 2020 Jun 11.

Department GF Ingrassia, University of Catania, Catania, Italy.

Brain Behav 2020 Jun 11:e01700. Epub 2020 Jun 11.

Department of Neurology, The Faculty of Health Sciences, Medical University of Warsaw, Warsaw, Poland.

Introduction: Speech disorder is a common clinical manifestation in patients with Parkinson's disease and atypical parkinsonian syndromes and tends to occur before the onset of the axial parkinsonian symptoms. Due to parkinsonian features that overlap those of Parkinson's disease, the differentiation of voice and a speech disorder is a challenge for clinicians primarily in the early stage of the disease.

Methods: Speech samples were obtained from 116 subjects including 30 cases of Parkinson's disease, 30 cases of progressive supranuclear palsy, 30 cases of multiple system atrophy, and control group consisted of 26 subjects. Read More

Curr Opin Neurol 2020 Jun 8. Epub 2020 Jun 8.

Department of Neurology, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Purpose Of Review: Progressive supranuclear palsy (PSP) is a progressive adult-onset neurodegenerative disease. Abnormally, phosphorylated forms of the microtubule-associated protein tau containing four repeat domains (4R-tau) aggregate in neurons. Additionally, increasing evidence suggests that secretion and uptake of fragments of abnormal 4R-tau may play a role in disease progression. Read More

Alzheimer Dis Assoc Disord 2020 Jun 9. Epub 2020 Jun 9.

Departments of Neurology.

Cerebrospinal fluid (CSF) amyloid-beta 1-42 (Aβ1-42) and amyloid positron emission tomography (PET) are the 2 main Alzheimer disease amyloid biomarkers that have been validated in neuropathologically confirmed Alzheimer disease cases. Although many studies have shown concordance of amyloid positivity or negativity between CSF Aβ1-42 and amyloid PET, several studies also reported discrepancies between these 2 Aβ biomarkers. We conducted a comparison of CSF Aβ1-42 level, amyloid PET, and autopsy findings in a case with progressive supranuclear palsy in which biomarker acquisition and postmortem pathologic examination were conducted almost at the same time. Read More

Sci Rep 2020 Jun 8;10(1):9161. Epub 2020 Jun 8.

Department of Neurology, Sant Pau Memory Unit, Hospital de la Santa Creu i Sant Pau - IIB Sant Pau, Barcelona, Spain.

Cerebrospinal fluid (CSF) biomarkers are useful in the diagnosis and the prediction of progression of several neurodegenerative diseases. Among them, CSF neurofilament light (NfL) protein has particular interest, as its levels reflect neuroaxonal degeneration, a common feature in various neurodegenerative diseases. In the present study, we analyzed NfL levels in the CSF of 535 participants of the SPIN (Sant Pau Initiative on Neurodegeneration) cohort including cognitively normal participants, patients with Alzheimer disease (AD), Down syndrome (DS), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Read More

PLoS One 2020 5;15(6):e0234265. Epub 2020 Jun 5.

La Trobe Centre for Sport and Exercise Medicine Research, School of Allied Health, Human Services & Sport, SHE College, La Trobe University, Bundoora, Australia.

Introduction: Progressive Supranuclear Palsy (PSP) is a debilitating form of atypical Parkinsonism. People living with PSP experience movement disorders affecting walking, balance and eye movements. The role of exercise in optimising movement remains unclear. Read More

Parkinsonism Relat Disord 2020 04 25;73:105-116. Epub 2020 May 25.

Department of Neurosciences, University of California San Diego, San Diego, CA, 92093, USA. Electronic address:

Progressive supranuclear palsy (PSP) is a complex clinicopathologic disease with no current cure or disease modulating therapies that can only be definitively confirmed at autopsy. Growing understanding of the phenotypic diversity of PSP has led to expanded clinical criteria and new insights into etiopathogenesis that coupled with improved in vivo biomarkers makes increased access to current clinical trials possible. Current standard-of-care treatment of PSP is multidisciplinary, supportive and symptomatic, and several trials of potentially disease modulating agents have already been completed with disappointing results. Read More

Chem Pharm Bull (Tokyo) 2020 ;68(6):526-533

Department of Chemistry and Life Science, College of Bioresource Sciences, Nihon University.

Inhibitors of human β-N-acetyl-D-hexosaminidase (hHEX) A and human O-GlcNAcase (hOGA) reportedly play roles in multiple diseases, suggesting their potential for pharmacological chaperone (PC) therapy of Sandhoff disease (SD) and Tay-Sachs disease (TSD), as lysosomal storage diseases, and Alzheimer's disease and progressive supranuclear palsy, respectively. In particular, hHEXA inhibitors as PCs have been shown to successfully enhance hHEXA levels, leading to the chronic form of SD and TSD. In the diagnosis of enzyme deficiencies in SD and TSD, artificial hHEXA substrates based on 4-methylumbelliferone as a fluorophore are available and generally used; however, they do not have sufficient performance to screen for potential inhibitors for a PC therapy from compound libraries. Read More

J Alzheimers Dis 2020 May 26. Epub 2020 May 26.

Department of Medicine, Center for Neurodegenerative diseases (CEMAND), Surgery and Dentistry, NeuroScience Section, University of Salerno, Italy.

Background: Mutations in the GRN gene are causative for an autosomal dominant form of frontotemporal dementia.

Objective/methods: The objective of the present study is to describe clinical and molecular features of three siblings harboring the GRN deletion NM_002087.3:c. Read More

Front Neurol 2020 8;11:395. Epub 2020 May 8.

Department of Neurology, St. Olavs Hospital, Trondheim, Norway.

The diagnosis of Parkinson's disease (PD) relies on the clinical effects of dopamine deficiency, including bradykinesia, rigidity and tremor, usually manifesting asymmetrically. Misdiagnosis is common, due to overlap of symptoms with other neurodegenerative disorders such as multiple system atrophy and progressive supranuclear palsy, and only autopsy can definitively confirm the disease. Motor deficits generally appear when 50-60% of dopaminergic neurons in the substantia nigra are already lost, limiting the effectiveness of potential neuroprotective therapies. Read More

Clin Nucl Med 2020 Jul;45(7):e311-e316

From the Department of Nuclear Medicine and PET/CT, Mahajan Imaging Centre.

FTLD (Frontotemporal lobar degeneration) is a clinically and pathologically heterogeneous group of degenerative disorders, characterized by predominantly asymmetric degeneration of frontal and temporal lobes with selective neuronal loss and gliosis. The disease presents with variable degrees of impairment in behavior, language, executive control, and motor symptoms with progressive loss of cognition. On the basis of presenting clinical symptoms, FTLD is further divided into behavioral variant, nonfluent/agrammatic variant primary progressive aphasia (PPA), semantic variant PPA, logopenic variant PPA, progressive supranuclear palsy, and corticobasal ganglionic degeneration. Read More

J Neurol Sci 2020 May 8;415:116891. Epub 2020 May 8.

Department of Neurology, National Institute of Mental Health & Neurosciences (NIMHANS), Hosur Road, Bangalore, Karnataka 560029, India. Electronic address:

Sleep disturbance is one of the commonly reported non-motor symptoms in patients with Parkinson's disease (PD) as well as in Parkinson plus disorders such as multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS). Although there is a wealth of literature on sleep disturbances in PD, the same is not robust on the Parkinson plus disorders. This article aims to comprehensively review the sleep disturbances in Parkinson plus disorders. Read More

Psychiatr Clin North Am 2020 Jun 8;43(2):345-360. Epub 2020 Apr 8.

UCSF Memory and Aging Center, Box 1207, 675 Nelson Rising Lane, Suite 190, San Francisco, CA 94143, USA. Electronic address: https://twitter.com/brucemillerucsf.

Frontotemporal dementia (FTD) encompasses a group of clinical syndromes, including behavioral-variant FTD, nonfluent variant primary progressive aphasia, semantic variant primary progressive aphasia, FTD motor neuron disease, progressive supranuclear palsy syndrome, and corticobasal syndrome. Early on in its course, FTD is commonly seen in psychiatric clinics. We review the clinical features and diagnostic criteria in FTD spectrum disorders. Read More

Psychiatr Clin North Am 2020 Jun 8;43(2):331-344. Epub 2020 Apr 8.

UCSF Memory and Aging Center, Box 1207, 675 Nelson Rising Lane, Suite 190, San Francisco, CA 94143, USA. Electronic address: https://twitter.com/brucemillerucsf.

Frontotemporal dementia (FTD) encompasses a group of clinical syndromes, including behavioral variant FTD, nonfluent variant primary progressive aphasia, semantic variant primary progressive aphasia, FTD motor neuron disease, progressive supranuclear palsy syndrome, and corticobasal syndrome. Early on in its course, FTD is commonly seen in psychiatric clinics. In this article the authors review the neuroimaging, pathology, genetics, and therapeutic interventions for FTD spectrum disorders. Read More

Brain 2020 May;143(5):1555-1571

Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

The syndromes caused by frontotemporal lobar degeneration have highly heterogeneous and overlapping clinical features. There has been great progress in the refinement of clinical diagnostic criteria in the past decade, but we propose that a better understanding of aetiology, pathophysiology and symptomatic treatments can arise from a transdiagnostic approach to clinical phenotype and brain morphometry. In a cross-sectional epidemiological study, we examined 310 patients with a syndrome likely to be caused by frontotemporal lobar degeneration, including behavioural variant frontotemporal dementia, non-fluent, and semantic variants of primary progressive aphasia (PPA), progressive supranuclear palsy and corticobasal syndrome. Read More

BMC Med Genomics 2020 May 19;13(1):71. Epub 2020 May 19.

Department of Microbiology, Immunology and Genetics; Graduate School of Biomedical Science, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX, USA.

Background: Methylation of mitochondrial tRNAs (mt-tRNA) at the 9th position ("p9 site") is known to impact translational efficiency and downstream mitochondrial function; however, direct assessment of mt-RNA methylation is challenging. Recent RNA sequence-based methods have been developed to reliably identify post-transcriptional methylation. Though p9 methylation has been studied in healthy human populations and in the context of cancer, it has not yet been analyzed in neurodegenerative disease, where mitochondrial dysfunction is a prominent and early hallmark of disease progression. Read More

Eur J Neurol 2020 May 16. Epub 2020 May 16.

Department of Neurology and Neurological Science, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, Tokyo, Japan.

Background And Purpose: Idiopathic normal pressure hydrocephalus (iNPH) is a clinical entity without established pathological hallmarks. Previous autopsy studies reported that patients with an antemortem diagnosis of iNPH had a different postmortem diagnosis, commonly progressive supranuclear palsy (PSP). Disproportionately enlarged subarachnoid space hydrocephalus (DESH) has been reported as a characteristic feature of iNPH on magnetic resonance imaging (MRI). Read More

Neurol India 2020 Mar-Apr;68(2):481-482

Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University; Department of Neurology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

In order to make a correct diagnosis of idiopathic Parkinson's disease (PD), it is essential to exclude atypical parkinsonian features, such as early dementia, fall, and autonomic dysfunction. Rheumatoid arthritis (RA), which is a systemic inflammatory disorder, although most patients present in a polyarticular manner. Still some may also present with extra-articular involvement including skin, lung, heart, and the central or peripheral nervous systems. Read More

Neurobiol Aging 2020 Sep 15;93:143.e5-143.e7. Epub 2020 Apr 15.

Institute of Molecular Bioimaging and Physiology, National Research Council, Section of Germaneto, Catanzaro, Italy.

DCTN1 encodes the largest subunit of dynactin complex essential in the retrograde axonal transport and cytoplasmic transport of vesicles; mutations in DCTN1 have been reported predominantly in individuals with Perry syndrome and, recently, in patients with progressive supranuclear palsy. Our genetic screening of DCTN1 in 79 patients with progressive supranuclear palsy, 100 patients with multiple system atrophy, and 28 patients with dementia with Lewy bodies from Italy revealed only synonymous and intronic variants, suggesting that DCTN1 mutations do not have a key role in the development of atypical parkinsonism in the Italian population. Read More

Mov Disord 2020 May 12. Epub 2020 May 12.

Neuroscience Research Center, University "Magna Graecia", Catanzaro, Italy.

Background: Idiopathic normal pressure hydrocephalus and PSP share several clinical and radiological features, making differential diagnosis, at times, challenging.

Objectives: To differentiate idiopathic normal pressure hydrocephalus from PSP using MR volumetric and linear measurements.

Methods: Twenty-seven idiopathic normal pressure hydrocephalus patients, 103 probable PSP patients, and 43 control subjects were consecutively enrolled. Read More

J Neurol 2020 Jun 11;267(6):1859-1863. Epub 2020 May 11.

Department of Medical, Surgical Sciences and Advanced Technologies GF Ingrassia, University of Catania, Via Santa Sofia 78, 95123, Catania, Italy.

Background: Differential diagnosis between Parkinson's disease (PD) and atypical Parkinsonian syndromes (APS), such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), is often difficult because of overlap of common clinical features. We evaluated R2 Blink Reflex Recovery Cycle (R2BRRC) in drug-naive PD patients and in MSA and PSP patients to differentiate early PD from APS.

Methods: We investigated 43 patients: 15 drug-naive PD patients, 16 MSA patients, and 12 PSP patients. Read More

J Clin Neurosci 2020 Jul 7;77:123-127. Epub 2020 May 7.

Department of Neurology, Medical University of Warsaw, Poland.

The aim of this work is to present whether SPECT Tc-HMPAO can be a method of examination to possibly differentiate the syndromes. 21 patients with PSP syndrome and 14 patients with corticobasal syndrome (CBS) were examined using SPECT Tc-HMPAO. Perfusion single photon emission computed tomography (SPECT) as a method of examination of progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) has not been extensively analyzed in contemporary literature. Read More

J Neurol 2020 May 9. Epub 2020 May 9.

Department of Neurology, Mayo Clinic College of Medicine and Science, 200 1st Street S.W., Rochester, MN, 55905, USA.

Objective: To describe I-FP-CIT (DAT scan) SPECT findings in progressive apraxia of speech (PAOS) patients and to compare those findings with progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS).

Background: PAOS is a neurodegenerative syndrome in which patients present with apraxia of speech, a motor speech disorder affecting programming and planning of speech. Patients with PAOS predictably develop Parkinsonism. Read More

Acta Neuropathol 2020 May 7. Epub 2020 May 7.

German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.

Progressive supranuclear palsy (PSP) is a 4R-tauopathy predominated by subcortical pathology in neurons, astrocytes, and oligodendroglia associated with various clinical phenotypes. In the present international study, we addressed the question of whether or not sequential distribution patterns can be recognized for PSP pathology. We evaluated heat maps and distribution patterns of neuronal, astroglial, and oligodendroglial tau pathologies and their combinations in different clinical subtypes of PSP in postmortem brains. Read More

Acta Radiol 2020 May 7:284185120920793. Epub 2020 May 7.

Department of Radiology, Huashan Hospital, Fudan University, Shanghai, PR China.

Background: Loss of swallow tail sign (STS) on iron-sensitive magnetic resonance imaging (MRI) has been recognized as an imaging feature in parkinsonism (PS).

Purpose: To investigate the diagnostic and differential diagnostic value of STS scale on susceptibility map-weighted imaging (SMWI) in PS, including Parkinson's disease (PD), progressive supranuclear palsy syndrome (PSP), and multiple system atrophy (MSA), and to evaluate its correlation with disease severity.

Material And Methods: Ninety-nine patients (55 PD, 29 PSP, and 15 MSA) and 47 healthy controls (HC) were prospectively recruited and scanned using quantitative susceptibility mapping (QSM). Read More

Neurosci Lett 2020 Jul 4;731:134919. Epub 2020 May 4.

Casma Therapeutics, Cambridge, MA, USA. Electronic address:

Tauopathies are a group of over 20 clinicopathological neurodegenerative diseases including Alzheimer's disease (AD), the most common type of dementia, progressive supranuclear palsy, Pick's disease, corticobasal degeneration, among others. Tauopathies are defined by neurodegeneration and the presence of tau aggregates in affected brains regions. Interestingly, regional tau aggregation burden correlates with clinical phenotype and predicts cognitive status. Read More

Mov Disord Clin Pract 2020 May 10;7(4):440-447. Epub 2020 Apr 10.

Memory and Aging Center, Department of Neurology University of California San Francisco California USA.

Background: Progressive supranuclear palsy (PSP) is a neurodegenerative disease without approved therapies, and therapeutics are often tried off-label in the hope of slowing disease progression. Results from these experiences are seldom shared, which limits evidence-based knowledge to guide future treatment decisions.

Objectives: To describe an open-label experience, including safety/tolerability, and longitudinal changes in biomarkers of disease progression in PSP-Richardson's syndrome (PSP-RS) patients treated with either salsalate or young plasma and compare to natural history data from previous multicenter studies. Read More

Cell Death Dis 2020 May 4;11(5):314. Epub 2020 May 4.

Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, TX, 77555, USA.

Tau aggregates propagate in brain cells and transmit to neighboring cells as well as anatomically connected brain regions by prion-like mechanisms. Soluble tau aggregates (tau oligomers) are the most toxic species that initiate neurodegeneration in tauopathies, such as Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and dementia with Lewy bodies (DLB). Exogenous tau aggregates have been shown to be internalized by brain cells; however, the precise cellular and molecular mechanisms that underlie the internalization of tau oligomers (TauO) remain elusive. Read More

Soc Cogn Affect Neurosci 2020 Jul;15(5):511-522

Berkeley Psychophysiology Laboratory, Department of Psychology, University of California, Berkeley, CA 94720-1650, USA.

Deficits in emotion perception (the ability to infer others' emotions accurately) can occur as a result of neurodegeneration. It remains unclear how different neurodegenerative diseases affect different forms of emotion perception. The present study compares performance on a dynamic tracking task of emotion perception (where participants track the changing valence of a film character's emotions) with performance on an emotion category labeling task (where participants label specific emotions portrayed by film characters) across seven diagnostic groups (N = 178) including Alzheimer's disease (AD), behavioral variant frontotemporal dementia (bvFTD), semantic variant primary progressive aphasia (svPPA), non-fluent variant primary progressive aphasia (nfvPPA), progressive supranuclear palsy (PSP), corticobasal syndrome and healthy controls. Read More

Mov Disord 2020 May 1. Epub 2020 May 1.

Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.

Objective: The objective of this study was to determine comprehensive metabolic changes of caffeine in the serum of patients with parkinsonian disorders including Parkinson's disease (PD), progressive supranuclear palsy (PSP), and multiple system atrophy (MSA) and to compare this with healthy control serum.

Methods: Serum levels of caffeine and its 11 downstream metabolites from independent double cohorts consisting of PD (n = 111, 160), PSP (n = 30, 19), MSA (n = 23, 17), and healthy controls (n = 43, 31) were examined by liquid chromatography-mass spectrometry. The association of each metabolite with clinical parameters and medication was investigated. Read More

Mov Disord 2020 May 1. Epub 2020 May 1.

Laboratory for Rehabilitation Neuroscience, Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, USA.

Objective: Accurate diagnosis is particularly challenging in Parkinson's disease (PD), multiple system atrophy (MSAp), and progressive supranuclear palsy (PSP). We compare the utility of 3 promising biomarkers to differentiate disease state and explain disease severity in parkinsonism: the Automated Imaging Differentiation in Parkinsonism (AID-P), the Magnetic Resonance Parkinsonism Index (MRPI), and plasma-based neurofilament light chain protein (NfL).

Methods: For each biomarker, the area under the curve (AUC) of receiver operating characteristic curves were quantified for PD versus MSAp/PSP and MSAp versus PSP and statistically compared. Read More

Alzheimer Dis Assoc Disord 2020 Apr 24. Epub 2020 Apr 24.

Third Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Subjectives: Lewy body dementia (LBD) is the second most common type of neurodegenerative dementia after Alzheimer disease (AD). It is characterized by the accumulation of Lewy bodies and Lewy neurites which are composed of aggregated phosphorylated alpha-synuclein, which is a presynaptic neuronal protein genetically and neuropathologically linked to Parkinson disease and to LBD. Alpha-synuclein is thought to contribute to LBD pathogenesis and to linked to disruption of cellular homeostasis and neuronal death, through effects on various intracellular targets, including synaptic function. Read More

Eur J Nucl Med Mol Imaging 2020 Apr 27. Epub 2020 Apr 27.

Department of Neurology, UMC Ljubljana, Zaloška cesta 2, 1000, Ljubljana, Slovenia.

Purpose: Differentiation among parkinsonian syndromes may be clinically challenging, especially at early disease stages. In this study, we used F-FDG-PET brain imaging combined with an automated image classification algorithm to classify parkinsonian patients as Parkinson's disease (PD) or as an atypical parkinsonian syndrome (APS) at the time when the clinical diagnosis was still uncertain. In addition to validating the algorithm, we assessed its utility in a "real-life" clinical setting. Read More

Orphanet J Rare Dis 2020 Apr 25;15(1):104. Epub 2020 Apr 25.

Institut Pediatric Hospital Sant Joan, Hospital Sant Joan de Déu, Passeig de Sant Joan de Deu, 2, 08950, Esplugues de Llobregat, Barcelona, Spain.

Background: Niemann-Pick disease Type C (NP-C) is a rare, progressive neurodegenerative disorder characterized by progressive neurodegeneration and premature death. We report data at closure of the NPC Registry that describes the natural history, disease course and treatment experience of NP-C patients in a real-world setting.

Methods: The NPC Registry was a prospective observational cohort study that ran between September 2009 and October 2017. Read More

Lancet Neurol 2020 05;19(5):422-433

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. Electronic address:

Background: CSF and PET biomarkers of amyloid β and tau accurately detect Alzheimer's disease pathology, but the invasiveness, high cost, and poor availability of these detection methods restrict their widespread use as clinical diagnostic tools. CSF tau phosphorylated at threonine 181 (p-tau181) is a highly specific biomarker for Alzheimer's disease pathology. We aimed to assess whether blood p-tau181 could be used as a biomarker for Alzheimer's disease and for prediction of cognitive decline and hippocampal atrophy. Read More

J Clin Neurol 2020 Apr;16(2):254-260

Department of Neurology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea.

Background And Purpose: Chopsticks are a primary eating utensil in East Asia, but systematic assessments of chopsticks skills in parkinsonian disorders is lacking. We aimed to identify any differences in chopsticks skills in the early stages of Parkinson's disease (PD) and atypical parkinsonism (AP), including progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal syndrome (CBS).

Methods: We consecutively recruited 111 patients with PD and 74 with AP (40 with PSP, 30 with MSA, and 4 with CBS) who were in a drug-naïve state. Read More

Eur J Nucl Med Mol Imaging 2020 Apr 21. Epub 2020 Apr 21.

Department of Nuclear Medicine, University Hospital of Munich LMU Munich, Marchioninstraße 15, 81377, Munich, Germany.

Purpose: Second-generation tau radiotracers for use with positron emission tomography (PET) have been developed for visualization of tau deposits in vivo. For several β-amyloid and first-generation tau-PET radiotracers, it has been shown that early-phase images can be used as a surrogate of neuronal injury. Therefore, we investigated the performance of early acquisitions of the novel tau-PET radiotracer [F]PI-2620 as a potential substitute for [F]fluorodeoxyglucose ([F]FDG). Read More

Parkinsonism Relat Disord 2020 May 15;74:74-75. Epub 2020 Apr 15.

German Center for Neurodegenerative Diseases (DZNE), Munich, Germany; Department of Neurology, Hannover Medical School, Hannover, Germany.

Neurol Clin Pract 2020 Apr;10(2):e17-e18

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.

Int J Neurosci 2020 Apr 16:1-3. Epub 2020 Apr 16.

Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, China.

Apraxia of eyelid opening (AEO) is a disabling syndrome characterized by inability to open the eyes at will, and patients occasionally attempt to open their eyes by contracting the frontalis muscles and touching their eye lids with their fingers. The exact pathophysiological mechanisms underlying this syndrome remain unknown. Previous reports suggest that AEO is often associated with blepharospasm and is occasionally seen in patients with Parkinson's disease or other movement disorders. Read More

Brain Pathol 2020 Jul 6;30(4):811-830. Epub 2020 May 6.

Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Granular/fuzzy astrocytes (GFAs), a subtype of "aging-related tau astrogliopathy," are noted in cases bearing various neurodegenerative diseases. However, the pathogenic significance of GFAs remains unclear. We immunohistochemically examined the frontal cortex, caudate nucleus, putamen and amygdala in 105 cases composed of argyrophilic grain disease cases (AGD, N = 26), and progressive supranuclear palsy (PSP, N = 10), Alzheimer's disease (AD, N = 20) and primary age-related tauopathy cases (PART, N = 18) lacking AGD, as well as 31 cases bearing other various neurodegenerative diseases to clarify (i) the distribution patterns of GFAs in AGD, and PSP, AD and PART lacking AGD, (ii) the impacts of major pathological factors and age on GFA formation and (iii) immunohistochemical features useful to understand the formation process of GFAs. Read More

Brain Nerve 2020 Apr;72(4):331-343

Hiroshima City Hiroshima Citizens Hospital.

Differentiating Parkinson's disease (PD) from multiple system atrophy with predominant parkinsonism (MSA-P) or progressive supranuclear palsy-parkinsonism (PSP-P) in early stages of the disease is extremely difficult. MSA-P and PSP-P are often misdiagnosed as PD. MSA-P and PSP-P may be diagnosed in their early stages by considering clinical symptoms and neuroradiological findings together. Read More