Ultrasensitive techniques and protein misfolding amplification assays for biomarker-guided reconceptualization of Alzheimer's and other neurodegenerative diseases.

Introduction: The clinical validation and qualification of biomarkers reflecting the complex pathophysiology of neurodegenerative diseases (NDDs) is a fundamental challenge for current drug discovery and development and next-generation clinical practice. Novel ultrasensitive detection techniques and protein misfolding amplification assays hold the potential to optimize and accelerate this process.

Areas Covered: Here we perform a PubMed-based state of the art review and perspective report on blood-based ultrasensitive detection techniques and protein misfolding amplification assays for biomarkers discovery and development in NDDs.

Mitochondrial D-Loop Region Methylation and Copy Number in Peripheral Blood DNA of Parkinson's Disease Patients.

Altered mitochondrial DNA (mtDNA) methylation has been detected in several human pathologies, although little attention has been given to neurodegenerative diseases. Recently, altered methylation levels of the mitochondrial displacement loop (D-loop) region, which regulates mtDNA replication, were observed in peripheral blood cells of Alzheimer's disease and amyotrophic lateral sclerosis patients. However, nothing is yet known about D-loop region methylation levels in peripheral blood of Parkinson's disease (PD) patients.

Progress regarding the context-of-use of tau as biomarker of Alzheimer's disease and other neurodegenerative diseases.

: Tau protein misfolding and accumulation in toxic species is a critical pathophysiological process of Alzheimer's disease (AD) and other neurodegenerative disorders (NDDs). Tau biomarkers, namely cerebrospinal fluid (CSF) total-tau (t-tau), 181-phosphorylated tau (p-tau), and tau-PET tracers, have been recently embedded in the diagnostic criteria for AD. Nevertheless, the role of tau as a diagnostic and prognostic biomarker for other NDDs remains controversial.

Is DAT imaging abnormality in normal pressure hydrocephalus always suggestive of degeneration?

Idiopathic normal pressure hydrocephalus (iNPH) is a debated entity with controversial pathogenesis, diagnostic criteria, and predictors of response after ventriculoperitoneal shunt (VPS). Parkinsonian signs are frequently reported in the clinical picture, sometimes due to the coexistence of an underlying neurodegenerative parkinsonism and sometimes in the absence thereof. To distinguish these two scenarios is crucial, since they may carry different long-term response to CSF drainage.

Cervical Dystonia Following Injury to the Cerebellar Pontine Angle: An Instructive Case.

A 38-year-old woman presented with cervical dystonia in the context of a recent surgery to remove a vestibular schwannoma. She initially presented to neurology with pain in the right arm, and MRI of the brain showed an incidental right-sided vestibular schwannoma (Video 1, Segment 1). An elective gamma-knife procedure was performed, which failed.

Quick Flicks: Association of Paroxysmal Kinesigenic Dyskinesia and Tics.

Background: Paroxysmal kinesigenic dyskinesia (PKD) is a rare disorder characterised by brief attacks of chorea, dystonia, or mixed forms precipitated by sudden movement.

Methods: Observational study with a cohort of 14 PKD patients and genetic testing for mutations.

Results: In a series of 14 PKD patients seen in our clinic at the National Hospital of Neurology, Queen Square, from 2012-2017, we noted tics in 11 patients (79%), which stand in stark contrast to the estimated lifetime prevalence of tics estimated to reach 1%.

Aerobic rehabilitation program for improving muscle function in Parkinson's disease.

Background: Parkinson's Disease (PD) is characterized by progressive and disabling symptoms. An impaired oxidative metabolism efficiency was supposed to be involved in the systemic impairment. Rehabilitative treatment represents a valid tool in promoting skeletal muscle's adaptations, even if no solid studies on muscle metabolic features are still available.