Brain-Derived Neurotrophic Factor (BDNF) and Serotonin Transporter (SERT) in Platelets of Patients with Mild Huntington's Disease: Relationships with Social Cognition Symptoms.

Deficits in social-cognition processing have been identified during early stages of Huntington Disease (HD), attracting interest on their relevance as possible predictors of  neurodegenerative progression. Since the neurotrophin Brain-Derived Neurotrophic Factor (BDNF) and the serotonin (5-HT) transporter (SERT) are known to modulate human adaptive behavior, we appraised these two proteins in mild-HD using blood platelets, with the aim at finding relationships with cognitive/psychosocial skills. Thirteen gene positive and symptomatic patients (9M/4W, HD-stage II, age> 40y) together 11 gender/age matched controls without a concurrent diagnosis of psychiatric disorders, underwent a blood test to determine BDNF storage and membrane-bound SERT in platelets by an ELISA immune-enzyme dosage and [3H]-paroxetine ([3H]-PAR) binding, respectively. Enrolled subjects were concurrently evaluated through a battery of socio-cognitive tests and emotion recognition questionnaires.Results showed greater intra-platelet BDNF (~ +20-22%) in patients versus controls, whereas equilibrium [3H]-PAR binding parameters, maximum density (Bmax) and dissociation constant (KD), did not appreciably vary in the two comparison groups. Cognitive/emotion abilities were found significantly reduced in patients. Additionally, platelet BDNF was unrelated to psycho-cognitive scores, but positively correlated with the illness duration. As well, SERT Bmax was unconnected to HD signs or socio-cognitive scores, whilst KDs negatively correlated with scores for angry voice recognition in both controls and patients. This pilot study suggests that platelet BDNF and SERT do not specifically underlie psychosocial deficits in stage II-HD, while higher BDNF storage in delayed mild symptoms, would derive from compensatory mechanisms. Supplementary investigations are warranted, by also comparing patients in other illness's phases.

Mild affective symptoms in de novo Parkinson's disease patients: relationship with dopaminergic dysfunction.

BACKGROUND AND PURPOSE: The investigation of the relationship between affective symptoms and dopamine transporter (DAT) density provided conflicting data in both Parkinson's disease (PD) and non-PD patients. However, the potential interference of psychoactive as well as anti-parkinsonian drugs on DAT density should be taken into account. OBJECTIVE: To investigate the relationship between affective symptoms and pre-synaptic dopaminergic function in de novo PD patients. METHODS: Forty-four de novo PD consecutive outpatients were recruited, and the severity of anxious symptoms was evaluated with the Hamilton Anxiety Rating Scale (HAM-A), the severity of depressive symptoms with the Hamilton Depression Scale (HAM-D) and the Beck Depression Inventory (BDI). Six patients had a formal diagnosis of depression. All patients performed (123) I-FP-CIT SPECT, and semi-quantitative striatal indices were calculated. RESULTS: Disease severity, as measured by Unified Parkinson's Disease Rating Scale (UPDRSIII), was inversely correlated with bilateral striatal indices. Bilateral striatal uptake was significantly positively correlated with HAM-D (r.329; r.423, respectively, right and left), BDI (r.377; r.360, respectively, right and left) and HAM-A (r.338; r.340, respectively, right and left). After controlling for age, disease duration and severity, and Mini Mental State Examination (MMSE), no significant reduction in r-values was observed (P < 0.05). CONCLUSION: Our data support the existence of a relationship between depressive and anxious symptoms and the striatal (123) I-FP-CIT uptake. The finding of an increased DAT density associated with mild affective symptoms could be due to the lack of compensatory mechanisms usually present in early PD, and/or it might have a pathogenic role in affective symptoms by reducing the dopaminergic tone in the synaptic cleft.

Positron emission tomography imaging in multiple sclerosis-current status and future applications.

BACKGROUND: Multiple Sclerosis (MS) is traditionally considered as a central nervous system (CNS) white matter inflammatory disease. However, recent studies have focused on the neurodegenerative aspects of the disease, which occur early in the pathological process, providing an opportunity for therapeutic intervention and application of neuroprotective strategies. The relationship between neural inflammation and cell death remains controversial. The recent development of new radiolabelled ligands provides positron emission tomography (PET) imaging with a role for studying early aspects of the MS pathology. METHODS: We provide an overview of current PET research in MS, particularly focussing on possible applications of new radioligands for studying inflammation and neurodegenerative processes. RESULTS: Pathological aspects of neuroinflammation, axonal degeneration and neuronal repair may be explored in vivo with selective PET tracers. Specific radioligands for the cannabinoid system may be applied in MS research to understand the role of this neurotransmitter system in the pathogenesis of the disease. CONCLUSIONS: PET imaging represents a promising tool for elucidating controversial aspects of MS pathology and for the assessment of selective and potentially neuroprotective therapies.

Differences in nigro-striatal impairment in clinical variants of early Parkinson's disease: evidence from a FP-CIT SPECT study.

INTRODUCTION: In idiopathic Parkinson's disease (PD), two different clinical phenotypes are usually distinguished: a tremor dominant variant (TD) and an akinetic-rigid type (ART). TD patients are characterized by a slower disease progression and a minor cognitive impairment. Striatal density of DAT, as quantified by FP-CIT SPECT, has been reported to correlate with rigidity and akinesia but not with tremor. OBJECTIVE: To evaluate FP-CIT uptake in TD and ART phenotypes. METHODS: We retrospectively evaluated from our database the pre-synaptic nigro-striatal function of 24 patients with TD-PD and 38 patients with ART-PD who underwent a FP-CIT SPECT within 1 year from disease onset. RESULTS: Disease duration, age at the time of SPECT scan and disease severity as measured with Unified Parkinson's Disease Rating scale part III (UPDRS III) were not statistically different between the two groups. Putamen contralateral to the most clinically affected side showed a lower FP-CIT uptake in ART patients compared to TD patients. No statistically significant differences emerged when considering bilateral caudate and ipsilateral putaminal uptake, as well as asymmetry indices and caudate/putamen ratios. FP-CIT contralateral putaminal uptake correlated with the severity of rigidity and hypokinesia but not with tremor. CONCLUSIONS: These data suggest that other neurotransmitter systems apart from the nigro-striatal dopaminergic system are involved in the generation of Parkinsonian tremor, and they are consistent with previous evidence of a lack of correlation between tremor severity and FP-CIT uptake. Putaminal relative sparing in TD patients could partially explain the slower disease progression reported in this PD phenotype.

Environmental factors and Parkinson's disease: a case-control study in the Tuscany region of Italy.

To date the aetiology of Parkinson's disease (PD) is unknown although both genetic susceptibility and environmental factors appear to play an important role in the development of the disease. Recent data have also indicated that chronic exposure to a common pesticide can reproduce the neurochemical, behavioral and neuropathological features of PD. The epidemiological studies previously carried on the prevalence of PD in population exposed to environmental factors have produced controversial results, probably because of different trial design and different analysis methods. A case-control retrospective study was conducted in a well-defined geographic area in Tuscany-Italy with the aim to identify environmental factors possibly related to PD. No significant difference between PD patients and control subjects was observed in time spent in rural or industrial residence, in well water drinking and in the exposure to herbicides and pesticides. A significant difference between patients with PD and controls was reported for cigarette smoking, controls resulting more likely cigarette smokers in comparison with PD patients. The present findings support the view of a protective effect of cigarette smoking and do not show any significant association between environmental factors and the risk of development of PD.

CSF phosporylated TAU protein levels correlate with cerebral glucose metabolism assessed with PET in Alzheimer's disease.

One major goal of drug development would be the establishment of biomarkers as objective indicators of normal biological and pathogenetic processes, or pharmacological response to a therapeutic intervention. A potential approach is to investigate proteins in CSF linked to key neuropathological features of Alzheimer's disease (AD). Recently CSF phosphorylated-Tau (p-Tau) levels have been reported to reflect neurofibrillary changes within the brain of patients with AD, however the use of serial CSF investigations in order to monitor the disease progression is not applicable. PET with FDG reveals characteristic patterns in AD patients, however so far no correlation between in vivo metabolic information and pathological features has been reported. In the present study, we tested whether CSF Tau levels correlate with metabolic rate for glucose consumption in a cohort of 28 AD patients. We found a statistically significative correlation between both CSF total and p-TAU protein and relative metabolic indexes obtained from 18FDG-PET scans in parietal, temporal and occipital lobes bilaterally. These results indicate the existence of a correlation between impairment of cerebral metabolism, estimated throughout FDG-PET, and CSF Tau protein levels.

Brain perfusion effects of cholinesterase inhibitors in Parkinson's disease with dementia.

Several evidences suggest that cholinergic deficits may significantly contribute to dementia in Parkinson's disease (PDD) and acetylcholinesterase inhibitors (ChEIs) have been reported to improve cognitive symptoms in PDD, without worsening parkinsonism. Nineteen PDD patients underwent brain perfusion SPECT with (99m)Tc-ethyl cysteinate dimer after 6 months ChEIs treatment in order to evaluate the functional correlates of clinical improvement. A clear-cut cognitive improvement was reported in PDD patients with a significant improvement of ADAS-cog total score as well as of subscores exploring executive functions (p<0.01). MMSE total score did not significantly change after ChEIs but the subscore of attention significantly improved after therapy (p<0.01). No difference in motor performance as evaluated by UPDRS was reported. SPM analysis showed a significant increase of perfusion (p < 0.0001) in bilateral cingulate, and frontal regions after ChEIs. Our data confirm the efficacy of ChEIs in the treatment of dementia associated with PD mainly on attention and executive functions, and the functional findings indicate that this cognitive improvement could be associated with a sort of pharmacological frontal "re-afferentation".

Dopamine transporter imaging study in parkinsonism occurring in fragile X premutation carriers.

The authors studied four patients with parkinsonism carrying the fragile X premutation using SPECT with ([23)I]FP-CIT. They found evidence of preserved presynaptic nigrostriatal function, suggesting that parkinsonism in the X fragile premutation might be related to postsynaptic dopaminergic changes or different neurotransmitter alterations.