Superiority of Formalin-Fixed Paraffin-Embedded Brain Tissue for in vitro Assessment of Progressive Supranuclear Palsy Tau Pathology With [F-18]PI-2620

Objectives: Autoradiography on brain tissue is used to validate binding targets of newly discovered radiotracers. The purpose of this study was to correlate quantification of autoradiography signal using the novel next-generation tau positron emission tomography (PET) radiotracer [18F]PI-2620 with immunohistochemically determined tau-protein load in both formalin-fixed paraffin-embedded (FFPE) and frozen tissue samples of patients with Alzheimer's disease (AD) and Progressive Supranuclear Palsy (PSP). Methods: We applied [18F]PI-2620 autoradiography to postmortem cortical brain samples of six patients with AD, five patients with PSP and five healthy controls, respectively. Binding intensity was compared between both tissue types and different disease entities. Autoradiography signal quantification (CWMR = cortex to white matter ratio) was correlated with the immunohistochemically assessed tau load (AT8-staining, %-area) for FFPE and frozen tissue samples in the different disease entities. Results: In AD tissue, relative cortical tracer binding was higher in frozen samples when compared to FFPE samples (CWMRfrozen vs. CWMRFFPE: 2.5-fold, p < 0.001), whereas the opposite was observed in PSP tissue (CWMRfrozen vs. CWMRFFPE: 0.8-fold, p = 0.004). In FFPE samples, [18F]PI-2620 autoradiography tracer binding and immunohistochemical tau load correlated significantly for both PSP (R = 0.641, p < 0.001) and AD tissue (R = 0.435, p = 0.016), indicating a high agreement of relative tracer binding with underlying pathology. In frozen tissue, the correlation between autoradiography and immunohistochemistry was only present in AD (R = 0.417, p = 0.014) but not in PSP tissue (R = −0.115, p = n.s.). Conclusion: Our head-to-head comparison indicates that FFPE samples show superiority over frozen samples for autoradiography assessment of PSP tau pathology by [18F]PI-2620. The [18F]PI-2620 autoradiography signal in FFPE samples reflects AT8 positive tau in samples of both PSP and AD patients

Pearls & Oy-sters: Ocular motor apraxia as essential differential diagnosis to supranuclear gaze palsy: Eyes up

Ocular motor apraxia (OA) is an inability to initiate voluntary saccades in a head-fixed position, while saccades can be initiated by the vestibulo-ocular reflex (indicating dysfunction in the frontal eye fields)

Alexithymia Is Associated with Reduced Quality of Life and Increased Caregiver Burden in Parkinson's Disease

Parkinson's disease (PD) is the second most frequent neurodegenerative disease of people who are beyond 50 years of age. People with PD (PwP) suffer from a large variety of motor and non-motor symptoms resulting in reduced health-related quality of life (HR-QoL). In the last two decades, alexithymia was identified as an additional non-motor symptom in PD. Alexithymia is defined as a cognitive affective disturbance resulting in difficulty to identify and distinguish feelings from bodily sensations of emotional arousal. In PD, the frequency of patients suffering of alexithymia is increased compared to healthy controls. The aim of the present study was to determine the relationship of alexithymia to HR-QoL of the PwP and caregiver burden of the corresponding caregiver. This cross-sectional questionnaire-based study used disease specific questionnaires for HR-QoL and caregiver burden. In total 119 PwP and their corresponding caregivers were included in the study. HR-QoL of the PwP correlated significantly with alexithymia (p < 0.001), especially the sub-components "identifying feelings" (p < 0.001) and "difficulties describing feelings" (p = 0.001). Caregiver burden also correlated significantly with PwP alexithymia (p < 0.001). However, caregiver burden was associated with sub-components "identifying feelings" (p < 0.008) and "external oriented thinking" (p < 0.004). These data support the importance of alexithymia as a non-motor symptom in PD.status: publishe

Detection of a Parkinson's Disease-Specific MicroRNA Signature in Nasal and Oral Swabs

BackgroundBiomaterials from oral and nasal swabs provide, in theory, a potential resource for biomarker development. However, their diagnostic value has not yet been investigated in the context of Parkinson's disease (PD) and associated conditions. ObjectiveWe have previously identified a PD-specific microRNA (miRNA) signature in gut biopsies. In this work, we aimed to investigate the expression of miRNAs in routine buccal (oral) and nasal swabs obtained from cases with idiopathic PD and isolated rapid eye movement sleep behavior disorder (iRBD), a prodromal symptom that often precedes & alpha;-synucleinopathies. We aimed to address their value as a diagnostic biomarker for PD and their mechanistic contribution to PD onset and progression. MethodsHealthy control cases (n = 28), cases with PD (n = 29), and cases with iRBD (n = 8) were prospectively recruited to undergo routine buccal and nasal swabs. Total RNA was extracted from the swab material, and the expression of a predefined set of miRNAs was quantified by quantitative real-time polymerase chain reaction. ResultsStatistical analysis revealed a significantly increased expression of hsa-miR-1260a in cases who had PD. Interestingly, hsa-miR-1260a expression levels correlated with diseases severity, as well as olfactory function, in the PD and iRBD cohorts. Mechanistically, hsa-miR-1260a segregated to Golgi-associated cellular processes with a potential role in mucosal plasma cells. Predicted hsa-miR-1260a target gene expression was reduced in iRBD and PD groups. ConclusionsOur work demonstrates oral and nasal swabs as a valuable biomarker pool in PD and associated neurodegenerative conditions. & COPY;2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Innovative therapeutic concepts of progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is an opportunistic viral disease of the brain-caused by human polyomavirus 2. It affects patients whose immune system is compromised by a corresponding underlying disease or by drugs. Patients with an underlying lymphoproliferative disease have the worst prognosis with a mortality rate of up to 90%. Several therapeutic strategies have been proposed but failed to show any benefit so far. Therefore, the primary therapeutic strategy aims to reconstitute the impaired immune system to generate an effective endogenous antiviral response. Recently, anti-PD-1 antibodies and application of allogeneic virus-specific T cells demonstrated promising effects on the outcome in individual PML patients. This article aims to provide a detailed overview of the literature with a focus on these two treatment approaches

Accuracy of the national institute for neurological disorders and stroke/society for progressive supranuclear palsy and neuroprotection and natural history in Parkinson plus syndromes criteria for the diagnosis of progressive supranuclear palsy

Autopsy is the diagnostic gold standard for progressive supranuclear palsy (PSP). The National Institute of Neurological Disorders and Stroke and Society for Progressive Supranuclear Palsy (NINDS-SPSP) criteria for the clinical diagnosis of probable PSP are thought to possess high specificity and low sensitivity. The NINDS-SPSP criteria for possible PSP are considered to increase sensitivity at the expense of specificity. The Neuroprotection and Natural History in Parkinson Plus Syndromes (NNIPPS) criteria are intended to improve sensitivity while maintaining high specificity. The aim of this study was to conduct a clinicopathological evaluation of the NINDS-SPSP and NNIPPS criteria in tertiary neurological centers. Defined clinical features and their year of onset were recorded by chart review in neuropathologically diagnosed patients with PSP, Parkinsons's disease (PD), MSA parkinsonism and corticobasal degeneration from four European brain banks. Fulfilment of the clinical diagnostic criteria was verified for each year after disease onset and for the final antemortem record. We analyzed 98 PSP patients and 46 disease controls. The NINDS-SPSP probable criteria yielded shorter time to diagnosis, slightly higher specificity and positive predictive value (PPV), and similar sensitivity, compared with the NNIPPS criteria. Unexpectedly, the NINDS-SPSP possible criteria yielded the lowest sensitivity, specificity, and PPV. A combination of NINDS-SPSP possible and probable criteria yielded the highest sensitivity. We suggest that the NINDS-SPSP probable criteria might be preferred for recruitment of patients for clinical trials, where an early and specific diagnosis is important. For routine clinical care, where high sensitivity is crucial, a combination of NINDS possible and probable criteria might be preferred. (c) 2013 Movement Disorder Societ

Outcomes of SARS-CoV-2 Infections in Patients With Neurodegenerative Diseases in the LEOSS Cohort

The impact of preexisting neurodegenerative diseases on superimposed SARS-CoV-2 infections remains controversial. Here we examined the course and outcome of SARS-CoV-2 infections in patients affected by Parkinson's disease (PD) or dementia compared to matched controls without neurodegenerative diseases in the LEOSS (Lean European Open Survey on SARS-CoV-2-infected patients) cohort, a large-scale prospective multicenter cohort study..

Cortical [F-18]PI-2620 Binding Differentiates Corticobasal Syndrome Subtypes

Background Corticobasal syndrome is associated with cerebral protein aggregates composed of 4-repeat (similar to 50% of cases) or mixed 3-repeat/4-repeat tau isoforms (similar to 25% of cases) or nontauopathies (similar to 25% of cases). Objectives The aim of this single-center study was to investigate the diagnostic value of the tau PET-ligand [F-18]PI-2620 in patients with corticobasal syndrome. Methods Forty-five patients (71.5 +/- 7.6 years) with corticobasal syndrome and 14 age-matched healthy controls underwent [F-18]PI-2620-PET. Beta-amyloid status was determined by cerebral beta-amyloid PET and/or CSF analysis. Subcortical and cortical [F-18]PI-2620 binding was quantitatively and visually compared between beta-amyloid-positive and -negative patients and controls. Regional [F-18]PI-2620 binding was correlated with clinical and demographic data. Results Twenty-four percent (11 of 45) were beta-amyloid-positive. Significantly elevated [F-18]PI-2620 distribution volume ratios were observed in both beta-amyloid-positive and beta-amyloid-negative patients versus controls in the dorsolateral prefrontal cortex and basal ganglia. Cortical [F-18]PI-2620 PET positivity was distinctly higher in beta-amyloid-positive compared with beta-amyloid-negative patients with pronounced involvement of the dorsolateral prefrontal cortex. Semiquantitative analysis of [F-18]PI-2620 PET revealed a sensitivity of 91% for beta-amyloid-positive and of 65% for beta-amyloid-negative cases, which is in excellent agreement with prior clinicopathological data. Regardless of beta-amyloid status, hemispheric lateralization of [F-18]PI-2620 signal reflected contralateral predominance of clinical disease severity. Conclusions Our data indicate a value of [F-18]PI-2620 for evaluating corticobasal syndrome, providing quantitatively and regionally distinct signals in beta-amyloid-positive as well as beta-amyloid-negative corticobasal syndrome. In corticobasal syndrome, [F-18]PI-2620 may potentially serve for a differential diagnosis and for monitoring disease progression. (c) 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Societ