Candidate biomarkers of multiple system atrophy in cerebrospinal fluid

Abstract

Multiple system atrophy (MSA) is a neurodegenerative disease that presents as an autonomic dysfunction in combination with varying degrees of parkinsonism and cerebellar ataxia. It comprises a pathologically widespread neuronal loss accompanied by gliosis in the basal ganglia, cerebellum, pons, inferior olivary nuclei, and spinal cord. As a rapidly progressive disorder, MSA develops with autonomic dysfunction and mobility problems in several years. These autonomic and motor function impairments severely disrupt the patients’ daily lives. Currently, the therapeutic management of this disease is only symptomatic. An early and accurate diagnosis is helpful not only in the clinical field but also in the research for new therapies. The biomarkers in cerebrospinal fluid (CSF) and serum facilitate the differential diagnosis of MSA when the disease is difficult to recognize based on the clinical features or even presymptomatic. This review will summarize the biomarkers present in CSF that are potential candidates to accurately differentiate MSA from other similar neurodegenerative disorders.

Hyperbaric oxygen ameliorates cognitive impairment in patients with Alzheimer's disease and amnestic mild cognitive impairment

“…Moreover, we found that chronic hypoxia can enhance the γ‐secretase activity to promote Aβ production through the downregulation of the DNA methyltransferase 3b to reduce the methylation at CpG sites in promoter region of genes of γ‐secretase components, indicating that chronic hypoxia can aggravate AD pathology through epigenetic modifications 5 . On the other hand, chronic hypoxia may upregulate protein kinases, including GSK‐3β and CDK5, and suppress phosphatase, PP2A, leading to an enhanced tau phosphorylation 48,49 . Because hypoxia is involved in AD pathogenesis, hyperbaric oxygen treatment targeting hypoxia may be helpful to delay or ameliorate the progression of AD.…”

A balance of noncanonical Semaphorin signaling from the cerebrospinal fluid regulates apical cell dynamics during corticogenesis

“…Soluble forms of Nrps have been previously reported in physiological and pathological contexts. In particular, Nrp1 in the CSF was proposed to be associated with Alzheimer’s disease and aging in humans ( 40 , 41 ). Soluble forms of Nrps in the CSF could arise from splice variants encoding forms devoid of transmembrane domains, similar to those previously described for both Nrp1 and Nrp2 ( 17 , 42 ).…”

An unconventional cerebrospinal fluid-derived Semaphorin-signalling regulates apical progenitor dynamics in the developing neocortex

“…Soluble forms of Nrps have been previously reported in physiological as well as pathological contexts 20 . Particularly, Nrp1 in the CSF was proposed to be associated with Alzheimer disease and aging in humans 48,49 . Soluble forms of Nrps in the CSF could arise from splice variants encoding forms devoid of transmembrane domains, like those previously described for both Nrp1 and Nrp2 19,50 .…”