Mutations in three genes (PSEN1, PSEN2, and APP) have been identified in patients with early-onset (<65years) Alzheimer's disease (AD). We performed a screening for mutations in the coding regions of presenilins, as well as exons 16 and 17 of the APP gene in a total of 231 patients from the Iberian peninsular with a clinical diagnosis of early onset AD (mean age at onset of 52.9 years; range 31-64). We found three novel mutations in PSEN1, one novel mutation in PSEN2, and a novel mutation in the APP gene. Four previously described mutations in PSEN1 were also found. The same analysis was carried in 121 elderly healthy controls from the Iberian peninsular, and a set of 130 individuals NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript from seven African populations belonging to the Centre d'Etude du Polymorphisme Humain-Human Genome Diversity Panel (CEPH-HGDP), in order to determine the extent of normal variability in these genes. Interestingly, in the latter series, we found five new nonsynonymous changes in all three genes and a presenilin 2 variant (R62H) that has been previously related to AD. In some of these mutations, the pathologic consequence is uncertain and needs further investigation. To address this question we propose and use a systematic algorithm to classify the putative pathology of AD mutations.

Previous studies addressed the antioxidant and anti-inflammatory role of compounds from green tea in different human tissues. Positive antioxidant and anti-inflammatory effects were described for brain tissues. Whether similar effects are observed in the skeletal muscle, green tea supplementation could be a strategy to reduce delayed onset muscle soreness resultant of exercise. Here we determine the effect of green tea extract supplementation on exercise-induced muscle soreness, muscle damage and oxidative stress. We performed a randomized triple blind placebo control study. Twenty non-trained men performed sessions of exercise to induce delayed onset muscle soreness in the triceps sural muscle group before and after 15 days of supplementation (500 mg/day) with green tea extract (n = 10) or a placebo (n = 10). Muscle soreness was evaluated using a visual scale. Blood samples were taken at different moments to determine serum blood markers of muscle damage, oxidative stress and antioxidant status. We found that exercise induced delayed onset muscle soreness. Supplementation reduced muscle damage but muscle soreness did not change. Plasma oxidative damage marker and antioxidant status did not show an effect of supplementation. As a conclusion, green tea extract supplementation did not reduce the sensation of delayed onset muscle soreness but reduces the marker of muscle damage after exercise. It suggests the green tea extract supplementation has positive effects on muscle recovery after strenuous exercise.

A main implication of cumulative fatigue is the muscle damage that impairs neuromuscular function and training adaptations. These negative effects may limit performance when athletes exercise in consecutive days. In this regard, antioxidant supplementation has gain popularity among athletes. Green tea supplementation has been advocated as a strategy to improve exercise recovery due to the activity of its catechins with high antioxidant and anti-inflammatory potential. Here we performed a triple blinded placebo control experiment to determine the effect of green tea extract (GTE) from Camellia sinensis on muscle damage, oxidative stress, and neuromuscular activity in athletes submitted to consecutive sessions of exercise and fatigue. Sixteen trained amateur male athletes were randomly assigned to a GTE supplemented (500 mg/day) or placebo group during 15 days. Effects of supplementation were tested during repeated trials of submaximal cycling at 60% of peak power output performed after a protocol for cumulative fatigue of knee extensors. Muscle damage and oxidative stress showed lower magnitudes in response to fatigue after GTE supplementation. Placebo group showed impaired neuromuscular activity and higher muscle damage and oxidative stress compared to the GTE group during the cycling trials under fatigue. In summary, GTE supplementation showed positive effects on neuromuscular function in response to a condition of cumulative fatigue. It suggests GTE supplementation may have potential to serve as a strategy to improve performance and recovery in conditions of cumulative exercise.

The clinical diagnosis of sporadic CreutzfeldtJakob disease (sCJD) is difficult, and reliable markers are highly desired. In this work we assess the value of several cerebrospinal fluid (CSF) markers for sCJD diagnosis. Within the framework of the Portuguese Epidemiological Surveillance Program for Human Prion Diseases, CSF samples from 71 patients with clinically suspected sCJD, 30 definite sCJD and 41 non-CJD patients, were analysed for the presence of 14-3-3 protein. CSF levels of tau (t-tau), and phosphorylated tau (p-tau181), S-100b and b amyloid (Ab42) proteins were determined. The influence of clinical and genetic characteristics on CSF markers sensitivity was also evaluated. Protein 14-3-3 was detected in 29/30 sCJD patients and 9/41 non-CJD patients. Extremely elevated t-tau and S-100b protein levels were found in sCJD patients, while p-tau181 levels were only slightly elevated and Ab42 showed no differences compared to controls. 14-3-3 was the most sensitive parameter (97%), but its specificity was low (78%); sensitivity/specificity for other proteins were: S-100b-93/93%, t-tau-93/95%, with maximum accuracy being obtained by a combination of tests (14-3-3 combined with either t-tau or S-100b, or combining S-100b with t-tau/Ab42 or p-tau/t-tau ratios). The sensitivity of 14-3-3, as well as of p-tau181/t-tau ratio, was decreased in younger patients with long disease duration, with the PrP-2 isotype and MV genotype. Both 14-3-3, t-tau and S-100b are sensitive markers for sCJD, but 14-3-3 specificity seems to be lower in this special clinical setting of rapidly progressing dementias. We propose that in cases with a 14-3-3 weak positive result, or in young patients with long disease duration, a second CSF marker would be valuable for the diagnosis of sCJD.

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