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Parkinsonism Relat Disord 2022 Jun 16;101:9-14. Epub 2022 Jun 16.

Department of Neurology, Mayo Clinic, Rochester, MN, USA. Electronic address:

Introduction: Multiple system atrophy (MSA) typically presents with parkinsonism, ataxia and/or autonomic dysfunction. Occasionally, clinically atypical (ca-MSA) cases masquerade as progressive supranuclear palsy (PSP). We aimed to investigate whether different neuroimaging modalities could facilitate differentiation and whether histopathologic characteristics could explain the atypical presentation. Read More

Z Gerontol Geriatr 2022 Jun 24. Epub 2022 Jun 24.

Klinikum Nürnberg, Paracelsus Medizinische Privatuniversität, Breslauerstr. 201, 90471, Nürnberg, Deutschland.

Atypical Parkinson syndromes represent a neuropathologically heterogeneous group and include the clinical entities dementia with Lewy bodies (DLB), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). The DLB and MSA are characterized by deposition of the protein alpha-synuclein (synucleinopathy), PSP and CBD are characterized by deposition of tau protein, often in the form of neurofibrillary tangles in nerve and glial cells (tauopathy). Misfolding and aggregation of the aforementioned proteins causes degeneration of the affected cell populations but the disease also spreads to anatomically neighboring brain regions, thus contributing to disease progression. Read More

Neuropathology 2022 Jun 23. Epub 2022 Jun 23.

London Neurodegenerative Diseases Brain Bank and Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Hexanucleotide repeat expansions in C9orf72 account for a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. There have been occasional reported cases associated with this expansion but also additional extrapyramidal clinical features. However, only very rarely has there been pathological confirmation of a parkinsonian syndrome associated with a C9orf72 repeat expansion. Read More

J Pers Med 2022 Jun 15;12(6). Epub 2022 Jun 15.

ARADyAL Instituto de Salud Carlos III, University Institute of Molecular Pathology Biomarkers, Universidad de Extremadura, E10071 Cáceres, Spain.

Coenzyme Q (CoQ) has an important role as an antioxidant. Being that oxidative stress is one of the mechanisms involved in the pathogenesis of Parkinson's disease (PD) and other neurodegenerative diseases, several studies addressed the concentrations of CoQ in the different tissues of patients with PD and other parkinsonian syndromes (PS), trying to elucidate their value as a marker of these diseases. Other studies addressed the potential therapeutic role of CoQ in PD and PS. Read More

Genes (Basel) 2022 Jun 9;13(6). Epub 2022 Jun 9.

Department of (Neuro)Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, 1105 AZ Amsterdam, The Netherlands.

To date, no neurodegenerative diseases (NDDs) have cures, and the underlying mechanism of their pathogenesis is undetermined. As miRNAs extensively regulate all biological processes and are crucial regulators of healthy brain function, miRNAs differentially expressed in NDDs may provide insight into the factors that contribute to the emergence of protein inclusions and the propagation of deleterious cellular environments. A meta-analysis of miRNAs dysregulated in Alzheimer's disease, Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies and frontotemporal lobar degeneration (TDP43 variant) was performed to determine if diseases within a proteinopathy have distinct or shared mechanisms of action leading to neuronal death, and if proteinopathies can be classified on the basis of their miRNA profiles. Read More

J Neurol Neurosurg Psychiatry 2022 Jun 22. Epub 2022 Jun 22.

Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.

Objectives: To explore the genetics of four Parkinson's disease (PD) subtypes that have been previously described in two large cohorts of patients with recently diagnosed PD. These subtypes came from a data-driven cluster analysis of phenotypic variables.

Methods: We looked at the frequency of genetic mutations in glucocerebrosidase (GBA) and leucine-rich repeat kinase 2 against our subtypes. Read More

Eur J Neurol 2022 Jun 14. Epub 2022 Jun 14.

Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Background: In the quest for in vivo diagnostic biomarkers to discriminate Parkinson's Disease (PD) from Progressive Supranuclear Palsy (PSP) and Multiple System Atrophy (MSA, mainly p phenotype), many advanced MRI techniques have been studied. Morphometric indexes, such as the Magnetic Resonance Parkinsonism Index (MRPI), demonstrated high diagnostic value in the comparison PD-PSP. The potential of Quantitative Susceptibility Mapping (QSM) was hypothesized, as increased magnetic susceptibility (Δχ) was reported in the red nucleus (RN) and medial part of substantia nigra (SNImed) of PSP patients, and in the putamen of MSA patients. Read More

Neurol Sci 2022 Jun 14. Epub 2022 Jun 14.

Nuclear Medicine Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, 50134, Florence, Italy.

Background: The early differential diagnosis among neurodegenerative parkinsonian disorders becomes essential to set up the correct clinical-therapeutic approach. The increased utilization of [F] fluoro-deoxy-glucose positron emission tomography (FDG PET) and the pressure for cost-effectiveness request a systematic evaluation and a validation of its utility in clinical practice. This retrospective study aims to consider the contribution, in terms of increasing accuracy and increasing diagnostic confidence, of voxel-based FDG PET analyses in the differential diagnosis of these disorders, including Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, and cortico-basal syndrome. Read More

J Neurol Neurosurg Psychiatry 2022 Jun 13. Epub 2022 Jun 13.

Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.

Corticobasal syndrome (CBS) is a clinical syndrome characterised by progressive asymmetric limb rigidity and apraxia with dystonia, myoclonus, cortical sensory loss and alien limb phenomenon. Corticobasal degeneration (CBD) is one of the most common underlying pathologies of CBS, but other disorders, such as progressive supranuclear palsy (PSP), Alzheimer's disease (AD) and frontotemporal lobar degeneration with TDP-43 inclusions, are also associated with this syndrome.In this review, we describe common and rare neuropathological findings in CBS, including tauopathies, synucleinopathies, TDP-43 proteinopathies, fused in sarcoma proteinopathy, prion disease (Creutzfeldt-Jakob disease) and cerebrovascular disease, based on a narrative review of the literature and clinicopathological studies from two brain banks. Read More

J Neural Transm (Vienna) 2022 Jun 13. Epub 2022 Jun 13.

Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.

To date, the diagnoses of Parkinson syndromes are based on clinical examination. Therefore, these specific diagnoses are made, when the neuropathological process is already advanced. However, disease modification or neuroprotection, is considered to be most effective before marked neurodegeneration has occurred. Read More

Expert Opin Investig Drugs 2022 Jun 13:1-11. Epub 2022 Jun 13.

Department of Neurosciences, University of California San Diego, San Diego, CA, USA.

Introduction: Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disease marked by a variety of movement, ocular, and cognitive symptoms. Currently, treatment is symptomatic, and there are no disease-modulating therapies. While clinical presentations can be variable, at autopsy, PSP shows 4-repeat (4 R) tau species that accumulate in brainstem, subcortical, and neocortical areas. Read More

J Neurosci Rural Pract 2022 Apr 7;13(2):276-282. Epub 2022 Apr 7.

Department of Neurology, SCB Medical College and Hospital, Cuttack, Odisha, India.

 The objectives of this study are (1) to describe the non-motor profile, the motor disability progression, and survival analysis of atypical parkinsonism in a tertiary care hospital of eastern India and (2) to elucidate the neurocircuitry and the putative substrates responsible for non-motor manifestations.  In this prospective observational study, patients were diagnosed based on Consensus Criteria for Progressive Supranuclear Palsy (PSP), The Fourth Consensus Report of the Dementia with Lewy Body (DLBD) Consortium 2017, The Autonomic Neuroscience 2018 Criteria for Multiple System Atrophy (MSA), and Armstrong 2013 Criteria for Corticobasal Degeneration (CBD). Disease severity was assessed at baseline and 6 months of follow-up using the Unified Parkinson's Disease Rating Scales (UPDRS). Read More

Front Neurol 2022 25;13:847798. Epub 2022 May 25.

INSERM U1043 - CNRS UMR 5282, INFINITY, Toulouse, France.

Background: Autoimmune encephalitis (AIE) is an increasingly broad nosological framework that may clinically mimic neurodegenerative diseases (NDDs).

Cases Reported: We describe here the clinical, radiological, electrophysiological, and biological evolution of three patients. Two women aged 73 and 72 years and a 69-year-old man presented with complex cognitive and focal neurological symptoms and each had a predominant frontal dysexecutive involvement and an unexpectedly high titer of anti-MAG antibodies in the serum and cerebrospinal fluid (CSF). Read More

Biomed J 2022 Jun 4. Epub 2022 Jun 4.

Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan; Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Keelung, Taiwan; Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan; Medical Imaging Research Center, Institute for Radiological Research, Chang Gung University/Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. Electronic address:

Background: There are currently no specific tests for either idiopathic Parkinson's disease or Parkinson-plus syndromes. The study aimed to investigate the diagnostic performance of features extracted from the whole brain using diffusion tensor imaging concerning parkinsonian disorders.

Materials And Methods: The retrospective data yielded 625 participants (average age: 61. Read More

J Korean Med Sci 2022 Jun 6;37(22):e183. Epub 2022 Jun 6.

Department of Neurology, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea.

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) overlap clinically with parkinsonism or extrapyramidal signs and pathologically with tauopathy. Asymmetric parkinsonism and cortical dysfunctions are classical features of CBD. However, symmetric parkinsonism, frequent falls, and supranuclear gaze palsy are key features of PSP. Read More

Brain Commun 2022 28;4(3):fcac108. Epub 2022 Apr 28.

Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 55905, USA.

Primary four-repeat tauopathies are characterized by depositions of the four-repeat isoform of the microtubule binding protein, tau. The two most common sporadic four-repeat tauopathies are progressive supranuclear palsy and corticobasal degeneration. Because tau PET tracers exhibit poor binding affinity to four-repeat pathology, determining how well MRI findings relate to underlying pathology is critical to evaluating their utility as surrogate markers to aid in diagnosis and as outcome measures for clinical trials. Read More

Acta Neuropathol Commun 2022 Jun 3;10(1):82. Epub 2022 Jun 3.

Roche Pharma Research and Early Development, Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center Basel, Grenzacherstrasse 124, 4070, Basel, Switzerland.

Based on immunostainings and biochemical analyses, certain post-translationally modified alpha-synuclein (aSyn) variants, including C-terminally truncated (CTT) and Serine-129 phosphorylated (pSer129) aSyn, are proposed to be involved in the pathogenesis of synucleinopathies such as Parkinson's disease with (PDD) and without dementia (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). However, quantitative information about aSyn proteoforms in the human brain in physiological and different pathological conditions is still limited. To address this, we generated sequential biochemical extracts of the substantia nigra, putamen and hippocampus from 28 donors diagnosed and neuropathologically-confirmed with different synucleinopathies (PD/PDD/DLB/MSA), as well as Alzheimer's disease, progressive supranuclear palsy, and aged normal subjects. Read More

NPJ Parkinsons Dis 2022 Jun 2;8(1):68. Epub 2022 Jun 2.

Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich, 52428, Jülich, Germany.

The pathological hallmark of neurodegenerative diseases is the formation of toxic oligomers by proteins such as alpha-synuclein (aSyn) or microtubule-associated protein tau (Tau). Consequently, such oligomers are promising biomarker candidates for diagnostics as well as drug development. However, measuring oligomers and other aggregates in human biofluids is still challenging as extreme sensitivity and specificity are required. Read More

Neuroepidemiology 2022 Jun 2. Epub 2022 Jun 2.

Introduction We estimated the point prevalence of progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) at regional and national levels in Scotland, UK as there are few high-quality prevalence studies of these conditions. Methods Nationally, multiple methods of case ascertainment were used including clinician and nurse specialist referral, searches of ICD-10 diagnostic coding in routinely collected electronic health data (Scottish Morbidity Record), and patient self-referral. In one region we also searched GP databases and unselected hospital correspondence. Read More

J Nucl Med 2022 Jun;63(Suppl 1):60S-67S

Neuroscience Discovery Research, Translational Imaging, AbbVie, North Chicago, Illinois.

PET technology has produced many radiopharmaceuticals that target specific brain proteins and other measures of brain function. Recently, a new approach has emerged to image synaptic density by targeting the synaptic vesicle protein 2A (SV2A), an integral glycoprotein in the membrane of synaptic vesicles and widely distributed throughout the brain. Multiple SV2A ligands have been developed and translated to human use. Read More

J Nucl Med 2022 Jun;63(Suppl 1):2S-12S

Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Since the invention of F-FDG as a neurochemical tracer in the 1970s, F-FDG PET has been used extensively for dementia research and clinical applications. FDG, a glucose analog, is transported into the brain via glucose transporters and metabolized in a concerted process involving astrocytes and neurons. Although the exact cellular mechanisms of glucose consumption are still under investigation, F-FDG PET can sensitively detect altered neuronal activity due to neurodegeneration. Read More

Parkinsonism Relat Disord 2022 Jun 22;99:84-90. Epub 2022 May 22.

Neuroscience Center, Magna Graecia University, Catanzaro, Italy; Neuroimaging Research Unit, Institute of Molecular Bioimaging and Physiology, National Research Council, Catanzaro, Italy. Electronic address:

Introduction: Progressive supranuclear palsy (PSP) patients show reduced amplitude and velocity of vertical saccades, but saccadic abnormalities have also been reported in Parkinson's disease (PD). We investigated amplitude and velocity of vertical saccades in PSP and PD patients, to establish the best video-oculographic (VOG) parameters for PSP diagnosis.

Methods: Fifty-one PSP patients, 113 PD patients and 40 controls were enrolled. Read More

Neurol Sci 2022 May 28. Epub 2022 May 28.

Grupo de Neurologia Cognitiva e do Comportamento, Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.

Background: Episodic memory impairment may occur in progressive supranuclear palsy (PSP). However, it remains uncertain whether this is due to executive dysfunction or to the involvement of brain areas responsible for memory.

Objectives: To investigate the specific brain regions underlying episodic memory impairment in PSP. Read More

J Clin Med 2022 May 10;11(10). Epub 2022 May 10.

Department of Nuclear Medicine, Mazovian Brodno Hospital, 03-242 Warsaw, Poland.

Differential diagnosis of progressive supranuclear palsy remains difficult, especially when it comes to the parkinsonism predominant type (PSP-P), which has a more favorable clinical course. In this entity, especially during the advanced stages, significant clinical overlaps with other tauopathic parkinsonian syndromes and multiple system atrophy (MSA) can be observed. Among the available additional diagnostic methods in every-day use, magnetic resonance imaging (MRI) focused specifically on the evaluation of the mesencephalon seems to be crucial as it is described as a parameter associated with PSP. Read More

Diagnostics (Basel) 2022 May 11;12(5). Epub 2022 May 11.

Department of Neurology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru 560029, India.

Progressive supranuclear palsy (PSP) is the second most common Parkinsonian disorder with complex etiology. The underlying molecular mechanism of PSP pathogenesis remains unclear. The present study aims to find the feasibility of using plasma miRNAs as novel biomarkers. Read More

Diagnostics (Basel) 2022 May 4;12(5). Epub 2022 May 4.

3rd Age Day Care Center, IASIS, 16562 Athens, Greece.

(1) Background: Considerable inconsistency exists regarding the neural substrates of anosognosia in dementia in previous neuroimaging studies. The purpose of this study was the evaluation of anosognosia perfusion correlates across various types of dementia using automated Brodmann areas (BAs) analysis and comparison with a database of normal subjects. (2) Methods: We studied 72 patients: 32 with Alzheimer's disease, 26 with frontotemporal dementia-FTD (12 behavioral FTD, 9 semantic FTD, 5 Progressive Non-Fluent Aphasia), 11 with corticobasal syndrome, and 3 with progressive supranuclear palsy. Read More

Neurology 2022 May 27. Epub 2022 May 27.

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

Background And Objectives: Motor speech function, including speech timing, is a key domain for diagnosing non-fluent/agrammatic variant primary progressive aphasia (nfvPPA). Yet, standard assessments employ subjective, specialist-dependent evaluations, undermining reliability and scalability. Moreover, few studies have examined relevant anatomo-clinical alterations in patients with pathologically-confirmed diagnoses. Read More

Exp Gerontol 2022 May 24;165:111842. Epub 2022 May 24.

Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.

Lewy body dementia encompasses the common neurodegenerative disorders Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). Lewy Body disease (LBD) is characterized by abnormal aggregates of α-synuclein (α-syn) in the brain which form Lewy bodies. LBD is commonly misdiagnosed/underdiagnosed, especially in early stages. Read More

Alzheimers Res Ther 2022 May 25;14(1):73. Epub 2022 May 25.

Department of Computer Science, Howard Hughes School of Engineering, University of Nevada Las Vegas (UNLV), Las Vegas, NV, USA.

Background: Drug development for neurodegenerative disorders (NDDs) is a long, complex, and expensive enterprise. Methods to optimize drug development for NDDs are needed. Basket trials have been widely used in oncology and have been promoted by the Food and Drug Administration as a means of enhancing the efficiency of drug development. Read More

Sci Adv 2022 May 25;8(21):eabm5029. Epub 2022 May 25.

Research Division of Dementia and Neurodegenerative Disease, Nagoya University Graduate School of Medicine, Nagoya, Japan.

While amyloid-β lies upstream of tau pathology in Alzheimer's disease, key drivers for other tauopathies, including progressive supranuclear palsy (PSP), are largely unknown. Various tau mutations are known to facilitate tau aggregation, but how the nonmutated tau, which most cases with PSP share, increases its propensity to aggregate in neurons and glial cells has remained elusive. Here, we identified genetic variations and protein abundance of filamin-A in the PSP brains without tau mutations. Read More