Alzheimer's disease (AD) is the most common type of dementia. In connection with the global trend of prolonging human life and the increasing number of elderly in the population, the AD becomes one of the most serious health and socioeconomic problems of the present. Tau protein promotes assembly and stabilizes microtubules, which contributes to the proper function of neuron. Alterations in the amount or the structure of tau protein can affect its role as a stabilizer of microtubules as well as some of the processes in which it is implicated. The molecular mechanisms governing tau aggregation are mainly represented by several posttranslational modifications that alter its structure and conformational state. Hence, abnormal phosphorylation and truncation of tau protein have gained attention as key mechanisms that become tau protein in a pathological entity. Evidences about the clinicopathological significance of phosphorylated and truncated tau have been documented during the progression of AD as well as their capacity to exert cytotoxicity when expressed in cell and animal models. This paper describes the normal structure and function of tau protein and its major alterations during its pathological aggregation in AD.

The principal aim of our study was to present norms for old and very old Czech adults on the Czech version of the Montreal Cognitive Assessment (MoCA) and investigate the influence of social and demographic factors on MoCA performance. We analyzed 540 adults aged ≥ 60 years (5-year age categories; nationally representative sample in terms of sex and educational level), who met strict inclusion criteria for the absence of neurodegenerative disorders and performed within normal range in neuropsychological assessment. Using multiple regression model, we found that MoCA performance was affected by age and education (both p < .001) but not sex. The study provides normed percentile estimates for MoCA performance stratified by age (60-74 years; ≥ 75 years) and education lower versus higher. We also present percentile equivalents for the MoCA and Mini-Mental State Examination (MMSE) for use in clinical practice. We found age- and education-related effects on MoCA performance which support the use of culturally adapted normative data.

This multi-center validation study identified the lack of preparation of accurate and consistent protein standards as the main reason for a poor inter-laboratory CV. This issue is also relevant to other protein biomarkers based on this type of assay and will need to be solved in order to achieve an acceptable level of analytical accuracy. The raw data of this study is available online.

SummaryThere is growing evidence of the involvement of advanced glycation end products (AGEs) in the pathogenesis of neurodegenerative processes including Alzheimer's disease (AD) and their function as a seed for the aggregation of Aβ, a hallmark feature of AD. AGEs are formed endogenously and exogenously during heating and irradiation of foods. We here examined the effect of a diet high in AGEs in the context of an irradiated diet on memory, insoluble Aβ42, AGEs levels in hippocampus, on expression of the receptor for AGEs (RAGE), and on oxidative stress in the vasculature. We found that AD‐like model mice on high‐AGE diet due to irradiation had significantly poorer memory, higher hippocampal levels of insoluble Aβ42 and AGEs as well as higher levels of oxidative stress on vascular walls, compared to littermates fed an isocaloric diet. These differences were not due to weight gain. The data were further supported by the overexpression of RAGE, which binds to Aβ42 and regulates its transport across the blood–brain barrier, suggesting a mediating pathway. Because exposure to AGEs can be diminished, these insights provide an important simple noninvasive potential therapeutic strategy for alleviating a major lifestyle‐linked disease epidemic.

There is accumulating evidence that training on working memory (WM) generalizes to other nontrained domains, and there are reports of transfer effects extending as far as to measures of fluid intelligence. Although there have been several demonstrations of such transfer effects in young adults and children, they have been difficult to demonstrate in older adults. In this study, we investigated the generalizing effects of an adaptive WM intervention on nontrained measures of WM and visuospatial skills. We randomly assigned healthy older adults to train on a verbal n-back task over the course of a month for either 10 or 20 sessions. Their performance change was compared with that of a control group. Our results revealed reliable group effects in nontrained standard clinical measures of WM and visuospatial skills in that both training groups outperformed the control group. We also observed a dose-response effect, that is, a positive relationship between training frequency and the gain in visuospatial skills; this finding was further confirmed by a positive correlation between training improvement and transfer. The improvements in visuospatial skills emerged even though the intervention was restricted to the verbal domain. Our work has important implications in that our data provide further evidence for plasticity of cognitive functions in old age.