In vivo Prevalence of Alzheimer Biomarkers in Dementia with Lewy Bodies.

BACKGROUND: Neuropathological studies indicate concomitant Alzheimer's disease (AD) pathology in patients with dementia with Lewy bodies (DLB). OBJECTIVES: To measure cerebrospinal fluid (CSF) levels of ß-amyloid peptide with 42 amino acids (Aß42), total tau protein (τT), and tau phosphorylated at threonine 181 (τP-181) in 38 patients fulfilling the diagnostic criteria of probable DLB according to the most recent (4th consensus) report. METHODS: Double-sandwich commercial ELISAs (Innotest; Fujirebio, Gent, Belgium) were used for measurements. RESULTS: According to the current cutoff values of our laboratory, 4 biomarker profiles were noted: abnormal levels of Aß42 only (44.7%), full AD profile (39.5%), abnormal levels of τT only (5.3%), and normal levels of all 3 biomarkers (10.5%). AD profile was associated with female sex, older age, lower education, and lower MMSE scores. CONCLUSIONS: Reduction in Αß42 in DLB may be more common (>80% of patients) than previously thought, and ∼40% may have the typical CSF AD biomarker profile. AD biochemistry in DLB may be an evolving process showing increasing frequency with disease progression.

Plasma glutamate and glycine levels in patients with amyotrophic lateral sclerosis.

Defective glutamate (Glu) metabolism and glutamate excitotoxicity have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Glycine (Gly), the main inhibitory neurotransmitter, has been shown to potentiate excitatory transmission. In the present study, the levels of Glu and Gly in fasting plasma were measured by high performance liquid chromatography (HPLC) in 20 healthy volunteers and in 65 untreated ALS patients. Increased plasma Glu levels were observed in ALS (p=0.05), correlating with longer disease duration (p=0.03, beta=0.34) and male gender (p=0.02). Furthermore, the increase was found only in the spinal subtype of the disease (p=0.03), while in the bulbar subtype, no significant increase was noted. As regards plasma Gly, no difference was observed between patients and controls; however female patients had higher levels than males. The above results are compatible with the "glutamate hypothesis" of ALS and suggest that the spinal and bulbar-onset subtypes of the disease may be biochemically different.

Oxidative damage to plasma proteins in patients with chronic alcohol dependence: the effect of smoking.

BACKGROUND: Accumulating evidence implicates oxidative stress in ethanol-induced toxicity. Ethanol has been reported to be involved in oxidative damage, mostly in vitro, or in post mortem tissues, while biochemical abnormalities in the blood or serum are scanty or lacking. The aim of the present study was to examine the oxidative status of plasma proteins as markers of oxidative stress in subjects with chronic alcohol dependence (CAD). Since smoking has also been associated with oxidative stress this factor was also considered. PATIENTS AND METHODS: A total of 71 patients with CAD and 61 healthy volunteers of comparable age were included in the study. The protein carbonyl assay was carried out in plasma, as a reliable measure of general oxidative protein damage, in these two groups. RESULTS: Increased plasma protein carbonyls (PCs) were found in patients with CAD as compared with the control group [mean values (nmollmg protein): 4.73+/-1.46 and 3.62+/-0.91 respectively, p<0.000001]. Within the control group, smokers had higher PCs than the non-smokers, however this difference was of marginal significance [mean values (nmol/mg protein): 3.93+/-1.32 and 3.47+/-0.63, respectively]. The CAD group had significantly increased PCs compared with both the smoker and the non-smoker subgroups of the controls (p<0.001 and p<0.0001, respectively). Duration of alcohol consumption, daily alcohol intake, smoke load, folic acid and vitamin B12 levels did not correlate significantly with PC levels. CONCLUSION: The above results support the evidence for systemic oxidative stress in CAD, which must be attributed mainly to alcohol consumption, while smoking may act synergistically.

CSF biomarkers ß-amyloid, tau proteins and a-synuclein in the differential diagnosis of Parkinson-plus syndromes.

INTRODUCTION: Differential diagnosis of Parkinson-plus patients (PSP, CBD, MSA) and Parkinson's disease (PD) patients is often not straightforward, particularly in atypical cases or at the initial stages of the diseases. Classic CSF biomarkers (amyloid-beta - Aß42, tau protein - τT and phosphorylated tau protein - τP-181) are established biomarkers in the diagnosis of Alzheimer's disease (AD). CSF a-synuclein (α-syn) has emerged as a promising biomarker in patients with Parkinsonism. The aim of this study was to analyze the CSF biochemical profile of patients with Parkinsonism. METHODS: We analyzed the CSF biomarker profile (Aß42, τT, τP-181, α-syn) and all relevant ratios in 68 patients with Parkinsonism (19 PSP, 15 MSA, 17 CBD, 17 PD) and 18 controls, diagnosed by latest established diagnostic criteria. RESULTS: CBD patients exhibited elevated τT and decreased Aß42 compared to the other groups. Five CBD, one PSP patient and one control had a typical AD CSF profile. After exclusion of these patients, the τT/Aß42 ratio was significantly elevated in MSA patients compared to PD patients and provided excellent specificity and adequate sensitivity in their differential diagnosis. CONCLUSION: CSF biochemical profile analysis is important in distinguishing AD patients with a CBS phenotype from non-AD CBS patients. The τT/Aß42 ratio is useful in the differential diagnosis of MSA from PD.

Add-on lamotrigine treatment and plasma glutamate levels in epilepsy: relation to treatment response.

We investigated the effects of add-on lamotrigine treatment on plasma glutamate (Glu) levels, in 29 epileptic patients. Plasma Glu levels were determined by high-performance liquid chromatography at baseline and at 1 and 3 months post-treatment. In patients with a seizure reduction of > or = 66% a decrease of Glu at month 1 was noted, followed by return to baseline levels at month 3. In the remaining patients a gradual increase of Glu was noted throughout the 3 months of the study. The above findings indicate that an excellent clinical response to add-on lamotrigine may be characterized by a statistically significant, yet transient decrease of plasma Glu levels, while increasing Glu levels may accompany a response that is moderate at best. The combination of lamotrigine with valproate was more frequent in patients with excellent clinical response and tended to result in glutamate decrease.

Plasma levels of antioxidant vitamins C and E are decreased in vascular parkinsonism.

Oxidative stress is an important mechanism of cell death in Parkinson's disease (PD) and brain ischemia. Vitamins C, E and A are important antioxidants and deficiency of these agents has been implicated in the mechanisms of atherosclerosis. We measured the levels of the above antioxidant vitamins in 44 patients with PD, 12 patients with vascular parkinsonism (VP), 11 patients with other parkinsonism syndromes of various causes and 39 controls. Vitamin A levels did not differ between groups. Vitamins C and E were found decreased in VP, while they were normal in PD indicating low levels of antioxidant vitamins in VP and stressing the necessity of maintaining sufficient dietary intake of these agents in the elderly.