Nucleic Acids-Based Biomarkers for Alzheimer's Disease Diagnosis and Novel Molecules to Treat the Disease.

Alzheimer's disease (AD) represents the most common form of dementia and affects million people worldwide, with a high social burden and considerable economic costs. AD diagnosis benefits from a well-established panel of laboratory tests that allow ruling-in patients, along with FDG and amyloid PET imaging tools. The main laboratory tests used to identify AD patients are Aß40, Aß42, the Aß42/Aß40 ratio, phosphorylated Tau 181 (pTau181) and total Tau (tTau). Although they are measured preferentially in the cerebrospinal fluid (CSF), some evidence about the possibility for blood-based determination to enter clinical practice is growing up. Unfortunately, CSF biomarkers for AD and, even more, the blood-based ones, present a few flaws, and twenty years of research in this field did not overcome these pitfalls. The tale even worsens when the issue of treating AD is addressed due to the lack of effective strategies despite the many decades of attempts by pharmaceutic industries and scientists. Amyloid-based drugs failed to stop the disease, and no neuroinflammation-based drugs have been demonstrated to work so far. Hence, only symptomatic therapy is available, with no disease-modifying treatment on hand. Such a desolate situation fully justifies the active search for novel biomarkers to be used as reliable tests for AD diagnosis and molecular targets for treating patients. Recently, a novel group of molecules has been identified to be used for AD diagnosis and follow-up, the nuclei acid-based biomarkers. Nucleic acid-based biomarkers are a composite group of extracellular molecules consisting of DNA and RNA alone or in combination with other molecules, including proteins. This review article reports the main findings from the studies carried out on these biomarkers during AD, and highlights their advantages and limitations.

Relapsing-Remitting Multiple Sclerosis diagnosis from cerebrospinal fluids via Fourier transform infrared spectroscopy coupled with multivariate analysis.

Multiple sclerosis (MS) is a chronic, progressive, inflammatory and degenerative disease of central nervous system. Here, we aimed to develop a method for differential diagnosis of Relapsing-Remitting MS (RRMS) and clinically isolated syndrome (CIS) patients, as well as to identify CIS patients who will progress to RRMS, from cerebrospinal fluid (CSF) by infrared (IR) spectroscopy and multivariate analysis. Spectral analyses demonstrated significant differences in the molecular contents, especially in the lipids and Z conformation of DNA of CSF from CIS, CIS to RRMS transformed (TCIS) and RRMS groups. These changes enables the discrimination of diseased groups and controls (individuals with no neurological disease) from each other using hierarchical cluster and principal component analysis. Some CIS samples were consistently clustered in RRMS class, which may indicate that these CIS patients potentially will transform to RRMS over time. Z-DNA band at 795 cm-1 that is existent only in diseased groups and significant increase in carbonyl amount, decrease in amideI/amide II and lipid/protein ratios observed only for RRMS groups can be used as diagnostic biomarkers. The results of the present study shed light on the early diagnosis of RRMS by IR spectroscopy complemented with multivariate analysis tools.

Circulating glioma biomarkers.

Validated biomarkers for patients suffering from gliomas are urgently needed for standardizing measurements of the effects of treatment in daily clinical practice and trials. Circulating body fluids offer easily accessible sources for such markers. This review highlights various categories of tumor-associated circulating biomarkers identified in blood and cerebrospinal fluid of glioma patients, including circulating tumor cells, exosomes, nucleic acids, proteins, and oncometabolites. The validation and potential clinical utility of these biomarkers is briefly discussed. Although many candidate circulating protein biomarkers were reported, none of these have reached the required validation to be introduced for clinical practice. Recent developments in tracing circulating tumor cells and their derivatives as exosomes and circulating nuclear acids may become more successful in providing useful biomarkers. It is to be expected that current technical developments will contribute to the finding and validation of circulating biomarkers.

Chlamydophila pneumoniae DNA and mRNA transcript levels in peripheral blood mononuclear cells and cerebrospinal fluid of patients with multiple sclerosis.

Chlamydophila pneumoniae DNA and mRNA transcripts were investigated by PCR and RT-PCR in fresh CSF and PBMC specimens co-cultured in Hep-2 cell lines and collected from 14 patients with definite RR MS and 19 patients with other inflammatory (OIND) and non-inflammatory (NIND) neurological controls. A positivity for C. pneumoniae DNA and mRNA was detected in CSF and PBMCs of 9 RR MS patients (64.2%) with evidence of disease activity, whereas only 3 controls were positive for Chlamydial DNA. These preliminary findings suggest that C. pneumoniae may occur in a persistent and metabolically active state at both peripheral and intrathecal levels in MS, but not in OIND and NIND.

[Detecting infectious agents in central nervous system inflammation by cerebrospinal fluid analysis]. / Liquoranalytik in der Diagnostik erregerbedingter Erkrankungen des Zentralnervensystems.

Cerebrospinal fluid analysis is the method of choice in CNS infection and provides the basis for appropriate treatment. Due to the proximity of CSF and CNS, the infectious agent may be detected directly by microscopy or antigen or nucleic acid detection--the latter by polymerase chain reaction--in native CSF or after culture. Furthermore, intrathecal antibody synthesis against the infectious agent may identify the cause of infection. This indirect antigen detection method requires correction for a systemic antibody response and a blood-CSF barrier disturbance. The following text gives an overview of appropriate detection methods and their relevance to the most important CNS infections.

[Nucleic acids of the cerebrospinal fluid in acute disorders of cerebral circulation]. / Nukleinovye kisloty likvora pri ostrykh narusheniiakh mozgovogo krovoobrashcheniia.

In normal subjects the overall contents of nucleic acids (NA) in the cerebrospinal fluid (CSF) was about 14 micrograms % of P as measured using the Spirin technique. This level was sharply increased in patients with stroke, cerebral arachnoiditis and brain tumors suggesting its possible use as an index in stroke differential diagnosis or a prognostic factor. Most substantial rise in NA levels (4 to 6-fold as compared with normal) was characteristic of the hemorrhagic stroke, the ischemic one eliciting only a rise by a factor of 2 to 3. In cases of a favorable outcome the CSF NA level was steadily decreasing, and in fatal cases it was increasing. The authors discuss the questions as to the sources of CSF NA in pathology, the nature and role of the nucleic factors in shaping the absorption spectra of the native CSF in a 250-300 nm band.