Active Amyloid-ß Vaccination Results in Epigenetic Changes in the Hippocampus of an Alzheimer's Disease-Like Mouse Model.

BACKGROUND: While evidence accumulates for a role of epigenetic modifications in the pathophysiological cascade of Alzheimer's disease (AD), amyloid-ß (Aß)-targeted active immunotherapy approaches are under investigation to prevent or slow the progression of AD. The impact of Aß active vaccines on epigenetic markers has not been studied thus far. OBJECTIVE: The current study aims to establish the relationship between active immunotherapy with a MER5101-based vaccine (consisting of Aß1-15 copies conjugated with a 7 aa spacer to the diphtheria toxoid carrier protein, formulated in a Th2-biased adjuvant) and epigenetic DNA modifications in the hippocampus of APPswe/PS1dE9 mice. METHODS: As we previously reported, immunotherapy started when the mice were 10 months of age and behavioral testing occurred at 14 months of age, after which the mice were sacrificed for further analysis of their brains. In this add-on study, global levels of DNA methylation and hydroxymethylation, and DNA methyltransferase 3A (DNMT3A) were determined using quantitative immunohistochemistry, and compared to our previously analyzed immunization-induced changes in AD-related neuropathology and cognition. RESULTS: Active immunization did not affect global DNA methylation levels but instead, resulted in decreased DNA hydroxymethylation and DNMT3A levels. Independent of immunization, inverse correlations with behavioral performance were observed for levels of DNA methylation and hydroxymethylation, as well as DNMT3A, while Aß pathology and synaptic markers did not correlate with DNA methylation levels but did positively correlate with DNA hydroxymethylation and levels of DNMT3A. CONCLUSION: Our results indicate that active Aß vaccination has significant effects on the epigenome in the hippocampus of APPswe/PS1dE9 mice, and suggest that DNA methylation and hydroxymethylation may be involved in cognitive functioning.

Daily symptom ratings for studying premenstrual dysphoric disorder: A review.

BACKGROUND: To review how daily symptom ratings have been used in research into premenstrual dysphoric disorder (PMDD), and to discuss opportunities for the future. METHODS: PsycINFO and Medline were systematically searched, resulting in the inclusion of 75 studies in which (1) participants met the diagnostic criteria for late luteal phase dysphoric disorder (LLPDD) or PMDD and (2) diaries were used to study LLPDD/PMDD. RESULTS: To date, diaries have been used to gain insight into the aetiology and phenomenology of PMDD, to examine associated biological factors, and to assess treatment efficacy. We found low consistency among the diaries used, and often only part of the menstrual cycle was analysed instead of the whole menstrual cycle. We also observed that there was substantial variability in diagnostic procedures and criteria. LIMITATIONS: This review excluded diary studies conducted in women with premenstrual syndrome, women seeking help for premenstrual complaints without a clear diagnosis, and women without premenstrual complaints. CONCLUSIONS: Prospective daily ratings of symptoms and related variables provide a valuable and important tool in the study of PMDD. This paper addresses some options for improving the use of diaries and proposes the use of experience sampling and ecological momentary assessment to investigate within-person variability in symptoms in more detail.

Behavioral and cognitive effects of tyrosine intake in healthy human adults.

The amino acid tyrosine is the precursor to the catecholamine neurotransmitters dopamine and norepinephrine. Increasing tyrosine uptake may positively influence catecholamine-related psychological functioning. We conducted a systematic review to examine the effects of tyrosine on behavior and cognition. Fifteen studies were reviewed. All studies except one involved tyrosine loading during a single test session. In most behavioral studies, there were no significant effects of tyrosine on exercise performance. In contrast, cognitive studies employing neuropsychological measures found that tyrosine loading acutely counteracts decrements in working memory and information processing that are induced by demanding situational conditions such as extreme weather or cognitive load. The buffering effects of tyrosine on cognition may be explained by tyrosine's ability to neutralize depleted brain catecholamine levels. There is evidence that tyrosine may benefit healthy individuals exposed to demanding situational conditions. For future research we recommend moving from studying the acute effects of a single tyrosine load in small samples to studying the behavioral and cognitive effects of tyrosine in larger groups over multiple weeks.