Biochemical aspects of dementias

Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies, and prion diseases are age-related neurodegenerative disorders associated with a progressive decline of cognitive brain functions. Due to the increase in prevalence rates, and the rising costs associated with clinical and social care, treatments designed to prevent or reverse these diseases are urgently needed. The most common major biochemical characteristic of these neurodegenerative diseases is the deposition of abnormal protein aggregates in brain. The decryption of the mechanisms of aggregation and associated neurotoxicity may reveal new therapeutic targets, which will enable treatment for these devastating conditions

Factors Driving Prosocial Online Behavior

In this article, we draw from the Social Identity Theory and the Theory of Reasoned Action to propose a research model that postulates Social Similarity, Perceived Status Enhancement, and Social Norm to be important drivers of people’s prosocial online behavior. We also provide an outlook on three experiments that we plan to use to evaluate our hypotheses. Overall, our study promises important practical implications for multiple parties such as non-governmental organizations and nonprofit organizations. More specifically, if successful, our study would emphasize the importance of several factors that would help drive prosocial online behavior: (1) matching beneficiaries with benefactors’ demographic background, (2) providing a functionality that enables benefactors to share their prosocial actions with others, and (3) displaying information about other benefactors

Proposing a Research Model for Slot Machine Usage

In this article, we combine the Technology Acceptance Model with social psychology research to propose a research model for slot machine usage. More specifically, we postulate positive influences of Perceived Usefulness, Perceived Enjoyment, Perceived Ease of Use, and Perceived Belonging on the Actual System Use of slot machines. Overall, we provide an interdisciplinary view on slot machine usage behavior that promises important practical implications for operators. Foremost, if confirmed, our hypotheses would suggest that operators need to focus on both utilitarian and hedonic aspects when designing/choosing their slot machines or gambling halls, and that they need to focus on factors driving people’s Perceived Belonging, such as friendly waitpersons, in order to (indirectly) drive the usage of slot machines

Histological markers in nasal mucosa of patients with Alzheimer's disease

Neuropathological changes such as dystrophic neurites and the presence of abnormal tau protein in the olfactory system, including primary sensory cells and nerve fibres have previously been demonstrated in nasal mucosa tissue of patients with Alzheimer's disease (AD). These changes were detected in autopsy-derived material from histopathologically confirmed AD cases as well as in biopsy tissue from clinical severely ill AD patients. To investigate the potential usefulness for the early diagnosis of AD, we obtained biopsy tissue from olfactory mucosa from 5 clinically mild to moderate AD patients and stained for the presence of tau or beta-amyloid by immunocytochemistry using a panel of specific antibodies. No positive staining was found in any of the cases. For comparison, post-mortem olfactory tissue from AD patients with severe neuropathological changes (widespread neurofibrillary tangles and amyloid in the brain) was investigated, in these severe cases, tau immunoreactivity was found in fine nerve fibres in the lamina propria and in a few olfactory epithelial cells. These results are consistent with other reports showing that cytoskeletal changes and tau pathology in the olfactory epithelium are not primary (or specific) features of AD and may occur predominantly in late stages of the disease

Trajectories of amyloid beta accumulation - Unveiling the relationship with APOE genotype and cognitive decline

Amyloid beta (Aβ) follows a sigmoidal time function with varying accumulation rates. We studied how the position on this function, reflected by different Aβ accumulation phases, influences APOE ɛ4's association with Aβ and cognitive decline in 503 participants without dementia using Aβ-PET imaging over 5.3-years. First, Aβ load and accumulation were analyzed irrespective of phases using linear mixed regression. Generally, ɛ4 carriers displayed a higher Aβ load. Moreover, Aβ normal (Aβ-) ɛ4 carriers demonstrated higher accumulation. Next, we categorized accumulation phases as "decrease", "stable", or "increase" based on trajectory shapes. After excluding the Aβ-/decrease participants from the initial regression, the difference in accumulation attributable to genotype among Aβ- individuals was no longer significant. Further analysis revealed that in increase phases, Aβ accumulation was higher among noncarriers, indicating a genotype-related timeline shift. Finally, cognitive decline was analyzed across phases and was already evident in the Aβ-/increase phase. Our results encourage early interventions for ɛ4 carriers and imply that monitoring accumulating Aβ- individuals might help identify those at risk for cognitive decline

The prion gene is associated with human long-term memory

Human cognitive processes are highly variable across individuals and are influenced by both genetic and environmental factors. Although genetic variations affect short-term memory in humans, it is unknown whether genetic variability has also an impact on long-term memory. Because prion-like conformational changes may be involved in the induction of long-lasting synaptic plasticity, we examined the impact of single-nucleotide polymorphisms (SNPs) of the prion protein gene (PRNP) on long-term memory in healthy young humans. SNPs in the genomic region of PRNP were associated with better long-term memory performance in two independent populations with different educational background. Among the examined PRNP SNPs, the common Met129Val polymorphism yielded the highest effect size. Twenty-four hours after a word list-learning task, carriers of either the 129MM or the 129MV genotype recalled 17% more information than 129VV carriers, but short-term memory was unaffected. These results suggest a role for the prion protein in the formation of long-term memory in human

Early β-amyloid accumulation in the brain is associated with peripheral T cell alterations

INTRODUCTION Fast and minimally invasive approaches for early diagnosis of Alzheimer's disease (AD) are highly anticipated. Evidence of adaptive immune cells responding to cerebral β-amyloidosis has raised the question of whether immune markers could be used as proxies for β-amyloid accumulation in the brain. METHODS Here, we apply multidimensional mass-cytometry combined with unbiased machine-learning techniques to immunophenotype peripheral blood mononuclear cells from a total of 251 participants in cross-sectional and longitudinal studies. RESULTS We show that increases in antigen-experienced adaptive immune cells in the blood, particularly CD45RA-reactivated T effector memory (TEMRA) cells, are associated with early accumulation of brain β-amyloid and with changes in plasma AD biomarkers in still cognitively healthy subjects. DISCUSSION Our results suggest that preclinical AD pathology is linked to systemic alterations of the adaptive immune system. These immunophenotype changes may help identify and develop novel diagnostic tools for early AD assessment and better understand clinical outcomes

SIMPL: Secure IoT Management Platform

The proliferation of IoT devices is increasing at a fast pace, whether for private or business use. However, despite their growing popularity, their safe operation is often not guaranteed. To tackle the security challenges of modern IoT environments, the German Federal Ministry of Education and Research is funding the SIMPL project in order to support research in this area. The contribution of this paper is to introduce the main goal, objectives, and key features of SIMPL

Automatic analysis of skull thickness, scalp-to-cortex distance and association with age and sex in cognitively normal elderly

Personalized neurostimulation has been a potential treatment for many brain diseases, which requires insights into brain/skull geometry. Here, we developed an open source efficient pipeline BrainCalculator for automatically computing the skull thickness map, scalp-to-cortex distance (SCD), and brain volume based on T $_{1}$ -weighted magnetic resonance imaging (MRI) data. We examined the influence of age and sex cross-sectionally in 407 cognitively normal older adults (71.9±8.0 years, 60.2% female) from the ADNI. We demonstrated the compatibility of our pipeline with commonly used preprocessing packages and found that BrainSuite Skullfinder was better suited for such automatic analysis compared to FSL Brain Extraction Tool 2 and SPM12- based unified segmentation using ground truth. We found that the sphenoid bone and temporal bone were thinnest among the skull regions in both females and males. There was no increase in regional minimum skull thickness with age except in the female sphenoid bone. No sex difference in minimum skull thickness or SCD was observed. Positive correlations between age and SCD were observed, faster in females (0.307%/y) than males (0.216%/y) in temporal SCD. A negative correlation was observed between age and whole brain volume computed based on brain surface (females -1.031%/y, males -0.998%/y). In conclusion, we developed an automatic pipeline for MR-based skull thickness map, SCD, and brain volume analysis and demonstrated the sex-dependent association between minimum regional skull thickness, SCD and brain volume with age. This pipeline might be useful for personalized neurostimulation planning

Radiation dosimetry and biodistribution of 11C-ABP688 measured in healthy volunteers

Introduction: In this study, we assessed the whole-body biodistribution and radiation dosimetry of the new glutamatergic ligand 11C-ABP688. This ligand binds specifically to the metabotropic glutamatergic receptor of subtype 5 (mGluR5). Materials and methods: The study included five healthy male volunteers aged 20-29years. After intravenous injection of 240-260MBq, a series of four to ten whole-body positron emission tomography/computed tomography scans were initiated, yielding 60-80min of data. Residence times were then calculated in the relevant organs, and the software packages Mirdose and Olinda were used to calculate the absorbed radiation dose and the effective dose equivalent. Results: Of the excreted 11C activity at 1hour, approximately 80% were eliminated via the hepato-biliary pathway and 20% through the urinary tract. The absorbed dose (mGy/MBq) was highest in the liver (1.64 E -2 ± 5.08 E -3), gallbladder (8.13 E -3 ± 5.6 E -3), and kidneys (7.27 E -3 ± 2.79 E -3). The effective dose equivalent was 3.68 ± 0.84microSv/MBq. Brain uptake in the areas with high mGluR5 density was 2-3 (SUV). The agreement between the values obtained from Mirdose and the Olinda was excellent. Conclusion: 11C-ABP688 is a very promising ligand for the investigation of mGluR5 receptors in humans. Brain uptake is high and the effective dose equivalent so low that serial examinations in the same subject seem feasibl