Prostaglandin D2 synthase and its post-translational modifications in neurological disorders

Prostaglandin D2 synthase (PGDS) (beta-trace protein) is a highly abundant cerebrospinal fluid (CSF) glycoprotein. A number of studies have been performed to determine the potential value of this protein for the diagnosis of various neurological disorders. The measurement of total PGDS levels in CSF has proved marginally useful for this purpose, but promising results were obtained while investigating changes in the posttranslational modifications (PTM) pattern. Using 2-DE analysis, we previously showed that PGDS is differentially expressed in ante- and post mortem CSF samples. In the present study, we examined whether the PGDS isoforms may help to distinguish stroke and neurodegenerative disease patients from healthy subjects. The pattern of PGDS PTM was analyzed in CSF from patients with various neurological disorders (n = 44) using IEF/immunoblotting techniques. Strong alterations of this pattern were detected in patients with different forms of degenerative dementia. These findings are consistent with PGDS being altered in some neurological diseases and provide new opportunities for clinical applications.     

Bioelectrochemical analysis of neurodegeneration: Refocusing efforts

Since 1970s, electrochemistry is enthusiastically used for studies of severe neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, or prion-associated transmissible spongiform encephalopathies, associated with the neuronal death in the brain. The existing electrochemical sensors can be used both for direct neurotransmitter analysis in the brain and for detection of both proteins/amyloid peptides and the extent of their aggregation/oligomerisation. However, these sensors' application in body fluids or certain brain areas of interest may be restricted by the presence of structurally or electrochemically related species interfering with electroanalysis. Thus, recent efforts are refocusing on bioelectroanalysis with the apatmer- and antibody-modified electrodes, enabling obtaining more specific, interference-free results that allow better correlations with the disease state. In this opinion, I consider these recent efforts aimed at deeper studies and better understanding of neurotransmitter and protein/peptide patterns linked to neurodegenerative disorders.     

Quantitative estimation of brain white matter abnormalities in elderly subjects using magnetic resonance imaging

Twenty-five elderly subjects were examined with brain magnetic resonance imaging (MRI). The subjects were divided into two groups: those with Mini-Mental State Examination (MMSE) scores above 25, and those subjects with MMSE scores between 18 and 24. The degree of white matter abnormalities (WMA) (expressed as relative volumes) as well as the presence of cerebrovascular risk factors were evaluated in the two groups. We found that a) subjects with low MMSE scores had significantly larger relative volumes of WMA than the subjects with higher scores, b) a significant correlation (r_s = 0.53, p < 0.009) between MMSE scores and the relative volume of WMA was also established, and c) a weak significant correlation (r_s = −0.51, p < 0.05) between arterial blood pressure and WMA was found in the subjects with high MMSE scores. Besides these findings no other correlations between the presence of cerebrovascular risk factors and WMA were found in any of the groups.     

Can we really ‘read’ art to see the changing brain? A review and empirical assessment of clinical case reports and published artworks for systematic evidence of quality and style changes linked to damage or neurodegenerative disease

The past three decades have seen multiple reports of people with neurodegenerative disorders, or other forms of changes in their brains, who also show putative changes in how they approach and produce visual art. Authors argue that these cases may provide a unique body of evidence, so-called ‘artistic signatures’ of neurodegenerative diseases, that might be used to understand disorders, provide diagnoses, be employed in treatment, create patterns of testable hypotheses for causative study, and also provide unique insight into the neurobiological linkages between the mind, brain, body, and the human penchant for art-making itself. However—before we can begin to meaningfully build from such emerging findings, much less formulate applications—not only is such evidence currently quite disparate and in need of systematic review, almost all case reports and artwork ratings are entirely subjective, based on authors' personal observations or a sparse collection of methods that may not best fit underlying research aims. This leads to the very real question of whether we might actually find patterns of systematic change if fit to a rigorous review—Can we really ‘read’ art to illuminate possible changes in the brain? How might we best approach this topic in future neuroscientific, clinical, and art-related research? This paper presents a review of this field and answer to these questions. We consider the current case reports for seven main disorders—Alzheimer's and Parkinson's disease, frontotemporal and Lewy body dementia, corticobasal degeneration, aphasia, as well as stroke—consolidating arguments for factors and changes related to art-making and critiquing past methods. Taking the published artworks from these papers, we then conduct our own assessment, employing computerized and human-rater-based approaches, which we argue represent best practice to identify stylistic or creativity/quality changes. We suggest, indeed, some evidence for systematic patterns in art-making for specific disorders and also find that case authors showed rather high agreement with our own assessments. More important, through opening this topic and past evidence to a systematic review, we hope to open a discussion and provide a theoretical and empirical foundation for future application and research on the intersection of art-making and the neurotypical, the changed, and the artistic brain.     

Integration of structural and functional magnetic resonance imaging improves mild cognitive impairment detection

The identification of mild cognitive impairments (MCI) via either structural magnetic resonance imaging (sMRI) or functional MRI (fMRI) has great potential due to the non-invasiveness of the techniques. Furthermore, these techniques allow longitudinal follow-ups of single subjects via repeated measurements. sMRI- or fMRI-based biomarkers have been adopted separately to diagnose MCI; however, there has not been a systematic effort to integrate sMRI- and fMRI-based features to increase MCI detection accuracy. This study investigated whether the detection of MCI can be improved via the integration of biomarkers identified from both sMRI and fMRI modalities. Regional volume sizes and neuronal activity levels of brains from MCI subjects were compared with those from healthy controls and used to identify biomarkers from sMRI and fMRI data, respectively. In the subsequent classification phase, MCI was automatically detected using a support vector machine algorithm that employed the identified sMRI- and fMRI-based biomarkers as an input feature vector. The results indicate that the fMRI-based biomarkers provided more information for detecting MCI than the sMRI-based biomarkers. Moreover, the integrated feature sets using the sMRI- and fMRI-based biomarkers consistently showed greater detection accuracy than the feature sets based only on the fMRI-based biomarkers. The results demonstrate that integration of sMRI and fMRI modalities can provide supplemental information to improve the diagnosis of MCI relative to either the sMRI or fMRI modalities alone.     

Imaging treatment effects in Alzheimer's disease

Alzheimer's disease (AD) is the commonest form of degenerative dementia and is characterised by progressive cognitive decline. Despite extensive research, the cause of AD is unknown and there is no cure at present. Of the deficits found in AD, that affecting the cholinergic neurotransmitter system is the best established and the only one translated into symptomatic treatment. Cholinergic enhancement with cholinesterase inhibitor (ChEI) drugs has been achieved and their efficacy and safety ascertained by conventional clinical trials. The mechanism of action of these drugs, however, is not well understood. Imaging with SPECT, PET, MRI and fMRI after treatment has clarified what happens in the brains of those AD patients treated with ChEI drugs. Studies with these techniques have identified increases in brain blood flow and glucose metabolism, restoration of nicotinic receptor function and re-establishment of task-related regional brain activation in response to cognitive stimulation after treatment. Structural MRI studies have explained, to some degree, why only a proportion of patients benefits from ChEI treatment and there is some evidence that some ChEI drugs might be neuroprotective. There are, however, many unsolved problems. Timing of treatment intervention to obtain maximum response and the determinants of treatment response are mostly unknown. It is also unclear whether administration of treatment in those patients who have no potential for response accelerates disease progression. These issues cannot be solved by conventional clinical trials. Pharmacoimaging studies could assist the development and refinement of drugs to treat those diseases, such as AD, which affect the central nervous system.     

Diffusion tensor MRI to investigate dementias: a brief review

Diffusion tensor magnetic resonance imaging (DT-MRI) is a powerful quantitative technique with the ability to detect in vivo microscopic characteristics and abnormalities of brain tissue. It has been successfully applied to a number of neurological conditions, such as stroke, multiple sclerosis and brain tumors, providing information otherwise inaccessible on the pathological substrates. DT-MRI has also been used to study patients with cognitive decline, mainly those with Alzheimer's disease. Several image-analysis approaches have been employed, including region of interest, histogram, voxel-based analyses and DT-MRI-based tractography. Specific patterns of spatial distribution of tissue damage and correlations with neuropsychological measures have been reported. This review focuses on the use of DT-MRI to investigate dementias. The main clinical results and the different methods of image analysis will be overviewed and discussed.     

Brain volumetrics to investigate aging and the principal forms of degenerative cognitive decline: a brief review

The volume of the brain and of some of its structures can provide insight into the pathological process of several diseases. For this reason, in the recent years we saw a tremendous progress in the development of automated techniques for gaining information about global and regional atrophy. This paper reviews the main methods of analysis to quantify brain volume, and their application to the study of normal aging and the principal forms of degenerative dementias.