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BackgroundNeurofibrillary pathology composed of tau protein is closely correlated with severity and phenotype of cognitive impairment in patients with Alzheimer’s disease and non-Alzheimer’s tauopathies. Targeting pathological tau proteins via immunotherapy is a promising strategy for disease-modifying treatment of Alzheimer’s disease. Previously, we reported a 24-week phase 1 trial on the active vaccine AADvac1 against pathological tau protein; here, we present the results of a further 72 weeks of follow-up on those patients.MethodsWe did a phase 1, 72-week, open-label study of AADvac1 in patients with mild to moderate Alzheimer’s disease who had completed the preceding phase 1 study. Patients who were previously treated with six doses of AADvac1 at monthly intervals received two booster doses at 24-week intervals. Patients who were previously treated with only three doses received another three doses at monthly intervals, and subsequently two boosters at 24-week intervals. The primary objective was the assessment of long-term safety of AADvac1 treatment. Secondary objectives included assessment of antibody titres, antibody isotype profile, capacity of the antibodies to bind to AD tau and AADvac1, development of titres of AADvac1-induced antibodies over time, and effect of booster doses; cognitive assessment via 11-item Alzheimer’s Disease Assessment Scale cognitive assessment (ADAS-Cog), Category Fluency Test and Controlled Oral Word Association Test; assessment of brain atrophy via magnetic resonance imaging (MRI) volumetry; and assessment of lymphocyte populations via flow cytometry.ResultsThe study was conducted between 18 March 2014 and 10 August 2016. Twenty-six patients who completed the previous study were enrolled. Five patients withdrew because of adverse events. One patient was withdrawn owing to noncompliance. The most common adverse events were injection site reactions (reported in 13 [50%] of vaccinated patients). No cases of meningoencephalitis or vasogenic oedema were observed. New micro-haemorrhages were observed only in one ApoE4 homozygote. All responders retained an immunoglobulin G (IgG) antibody response against the tau peptide component of AADvac1 over 6 months without administration, with titres regressing to a median 15.8% of titres attained after the initial six-dose vaccination regimen. Booster doses restored previous IgG levels. Hippocampal atrophy rate was lower in patients with high IgG levels; a similar relationship was observed in cognitive assessment.ConclusionsAADvac1 displayed a benign safety profile. The evolution of IgG titres over vaccination-free periods warrants a more frequent booster dose regimen. The tendency towards slower atrophy in MRI evaluation and less of a decline in cognitive assessment in patients with high titres is encouraging. Further trials are required to expand the safety database and to establish proof of clinical efficacy of AADvac1.Trial registrationThe studies are registered with the EU Clinical Trials Register and ClinicalTrials.gov: the preceding fi...

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Conditions predisposing to metabolic syndrome (MetS) are associated with increased oxidative stress and inflammation. We studied, in vegetarians (n = 90) and omnivores (n = 46), the impact of the dietary regimen on the occurrence of MetS risk factors (RFs: BMI, blood pressure, glucose metabolism and lipid profile) in relation to oxidative status (advanced glycation end products (AGEs), advanced oxidation protein products (AOPPs), malondialdehyde, ferric reducing ability of plasma, vitamins A, E, C, beta-carotene and superoxide dismutase activity) and microinflammation (C-reactive protein, leukocytes and neopterin). The proportion of subjects without/positive for one or two MetS RFs was comparable between the groups. From the components of MetS only immunoreactive insulin levels differed significantly (95% CI: omnivores: 5.0-7.1 microU/mL, vegetarians: 4.5-5.4, p = 0.03). Omnivores had lower AOPP (omnivores: 0.29-0.36 micromol/g albumin, vegetarians: 0.36-0.52, p = 0.01) and beta-carotene levels than vegetarians, they consumed more calories, proteins, fat and saturated fatty acids, and less fibres, beta-carotene and vitamin C. Multiple regression analysis revealed vitamin E and AOPP levels as the most important independent determinants of MetS RFs. The vegetarian diet seems to exert beneficial effects on MetS RFs associated microinflammation. Whether the vegetarian diet may counteract the deleterious effects of elevated AOPPs and AGEs, remains to be elucidated.

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