Electroencephalography can Ubiquitously Delineate the Brain Dysfunction of Neurodegenerative Dementia by Both Visual and Automatic Analysis Methods: A Preliminary Study.

Introduction: The aim was to examine the differences in electroencephalography (EEG) findings by visual and automated quantitative analyses between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD). Methods: EEG data of 20 patients with AD and 24 with DLB/PDD (12 DLB and 12 PDD) were retrospectively analyzed. Based on the awake EEG, the posterior dominant rhythm frequency and proportion of patients who showed intermittent focal and diffuse slow waves (IDS) were visually and automatically compared between the AD and DLB/PDD groups. Results: On visual analysis, patients with DLB/PDD showed a lower PDR frequency than patients with AD. In patients with PDR <8 Hz and occipital slow waves or patients with PDR <8 Hz and IDS, DLB/PDD was highly suspected (PPV 100%) and AD was unlikely (PPV 0%). On automatic analysis, the findings of the PDR were similar to those on visual analysis. Comparisons between visual and automatic analysis showed an overlap in the focal slow wave commonly detected by both methods in 10 of 44 patients, and concordant presence or absence of IDS in 29 of 43 patients. With respect to PDR <8 Hz and the combination of PDR <8 Hz and IDS, PPV and NPV in DLB/PDD and AD were not different between visual and automatic analysis. Conclusions: As the noninvasive, widely available clinical tool of low expense, visual analysis of EEG findings provided highly sufficient information to delineate different brain dysfunction in AD and DLB/PDD, and automatic EEG analysis could support visual analysis especially about PD.

Why do male nurses choose to work in foreign countries? A qualitative study on Chinese male nurses working in Japan.

Aim: This study aimed to examine foreign-educated male nurses' motivation to emigrate for work, as well as explore the contextual factors that shape their career trajectories. Background: To that end, we interviewed Chinese male nurses working in Japan. No previous study has examined why male nurses seek employment abroad or the problems they face. Methods: This study employed a qualitative and inductive research design. Sixteen Chinese male nurses working in Eastern and Western Japan were recruited using convenience and snowball sampling methods and were interviewed via video calls. Co-researchers of both genders from different occupational and cultural backgrounds coded the findings and identified common themes in participants' responses. We analysed our findings vis-à-vis various theoretical perspectives and developed an explanatory model. Results: Participants' experience as nurses in Japan ranged from six months to eight years. The findings confirmed that factors identified in earlier reports influenced nurses' motivation and work. Two new factors emerged: influence by others and social reasons. Moreover, two factors that affected male nurses' motivation to work abroad, namely, external factors and the influence of others, were identified. Social reasons were identified as a pull factor. Conclusion: Our study provides valuable insights into recruiting and retaining foreign male nurses in developed countries facing issues such as ageing populations and nursing shortages. Implications for nursing policy: This study has important implications for nursing management. Our findings highlight the importance of orienting foreign-educated nurses regarding the local work culture to increase the recruitment and retention of foreign talent. Moreover, enhanced salary packages and benefits to improve motivation can lead to improved job performance, which can positively impact patient and safety outcomes.

Acute inhibition of AMPA receptors by perampanel reduces amyloid ß-protein levels by suppressing ß-cleavage of APP in Alzheimer's disease models.

Hippocampal hyperexcitability is a promising therapeutic target to prevent Aß deposition in AD since enhanced neuronal activity promotes presynaptic Aß production and release. This article highlights the potential application of perampanel (PER), an AMPA receptor (AMPAR) antagonist approved for partial seizures, as a therapeutic agent for AD. Using transgenic AD mice combined with in vivo brain microdialysis and primary neurons under oligomeric Aß-evoked neuronal hyperexcitability, the acute effects of PER on Aß metabolism were investigated. A single oral administration of PER rapidly decreased ISF Aß40 and Aß42 levels in the hippocampus of J20, APP transgenic mice, without affecting the Aß40 /Aß42 ratio; 5 mg/kg PER resulted in declines of 20% and 31%, respectively. Moreover, PER-treated J20 manifested a marked decrease in hippocampal APP ßCTF levels with increased FL-APP levels. Consistently, acute treatment of PER reduced sAPPß levels, a direct byproduct of ß-cleavage of APP, released to the medium in primary neuronal cultures under oligomeric Aß-induced neuronal hyperexcitability. To further evaluate the effect of PER on ISF Aß clearance, a γ-secretase inhibitor was administered to J20 1 h after PER treatment. PER did not influence the elimination of ISF Aß, indicating that the acute effect of PER is predominantly on Aß production. In conclusion, acute treatment of PER reduces Aß production by suppressing ß-cleavage of amyloid-ß precursor protein effectively, indicating a potential effect of PER against Aß pathology in AD.

The relationship between hospital ethical climate and continuing education in nursing ethics.

BACKGROUND: In recent years, there has been a growing interest in the importance of creating a healthy ethical climate. Although relationship with various factors and the ethical climate have been reported, understanding of the relationship between ethical education and ethical climate is limited. AIM: This study aims to investigate the relationship between ethical climate, personal characteristics, and continuing education for ethics. METHODS: This study conducted a quantitative cross-sectional survey of 605 nurses in 3 teaching hospitals in Japan. Multiple-regression analysis was used to assess the relationship between ethical climate and demographic characteristics and continuing education. Further mean of ethical climate scores were compared between received continuing education and did not, using analysis of covariance adjusted for demographic variables. FINDINGS: The ethical climate showed significant association with hospital, gender, specialty of the unit, experience of ethics education, in-service ethical training, and workshops/ academic conferences on nursing ethics. In multiple-regression analysis, attending in-service ethical training increased the mean of ethical climate score (p = 0.031) and workshops/ academic conferences decreased the mean score (p = 0.028). Adjusted-mean of ethical climate score of nurses who had in-service training was significantly higher than those who had not (p = 0.038), whereas adjusted-mean of it of nurses who had attended workshops/ academic conferences was significant lower (p = 0.033). DISCUSSION: In-service training on ethics was associated with the positive ethical climate. Hospital should enhance ethical education. CONCLUSION: Ethical climate related to the nurses' personal characteristics and continuing education. We propose that organizational support for ethical education may be effective in raising the ethical climate of the workplace.

Speedometer-reading performance of senior drivers with cognitive impairment: a comparison of analogue and digital speedometers.

BACKGROUND: With the deterioration of cognitive functions, the capability to obtain information with speed, one of the essential elements needed to perform safe driving, may be impacted. We aimed to compare the legibility of analogue and digital speedometers for senior drivers with cognitive impairment, and examined the demographic, cognitive, and driving-related variables that predict their speedometer-reading performance. METHODS: A total of 50 senior drivers with cognitive impairment were investigated and asked to complete an office-based speedometer-reading test using an iPad. Two general types of speedometers (analogue and digital) were tested in this study. RESULTS: The age of the participants ranged from 61 to 92 years (mean (SD), 79.10 (6.973)), and 29 were male. The mean (SD) score of the Mini-Mental State Examination was 22.48 (6.089). The median (QL , QU ) scores of the analogue and digital speedometer-reading tests were 4 (4, 5.25) and 6 (6), respectively. Based on the result of the Wilcoxon signed-rank test, the score of the digital speedometer-reading test was significantly higher than that of the analogue one (Z = 4.399, P < 0.001). The results of multiple linear regression analyses show that the scores of the Mini-Mental State Examination (ß = 0.358, P = 0.025), and the trail-making test-A (ß = -0.443, P = 0.006) predicted the digital speedometer-reading performance, and they together explain 54.7% of the total variance. CONCLUSIONS: A digital speedometer was found to be easier for absolute value reading for senior drivers with cognitive impairment, compared to an analogue speedometer. Senior drivers with subjective cognitive decline may also have impairments in obtaining the speed information through an analogue speedometer. General cognitive function and attention may influence the speed-reading performance on the digital speedometer.

Failure of DNA double-strand break repair by tau mediates Alzheimer's disease pathology in vitro.

DNA double-strand break (DSB) is the most severe form of DNA damage and accumulates with age, in which cytoskeletal proteins are polymerized to repair DSB in dividing cells. Since tau is a microtubule-associated protein, we investigate whether DSB is involved in tau pathologies in Alzheimer's disease (AD). First, immunohistochemistry reveals the frequent coexistence of DSB and phosphorylated tau in the cortex of AD patients. In vitro studies using primary mouse cortical neurons show that non-p-tau accumulates perinuclearly together with the tubulin after DSB induction with etoposide, followed by the accumulation of phosphorylated tau. Moreover, the knockdown of endogenous tau exacerbates DSB in neurons, suggesting the protective role of tau on DNA repair. Interestingly, synergistic exposure of neurons to microtubule disassembly and the DSB strikingly augments aberrant p-tau aggregation and apoptosis. These data suggest that DSB plays a pivotal role in AD-tau pathology and that the failure of DSB repair leads to tauopathy.

Analysis of the Clock-Reading Ability in Patients with Cognitive Impairment: Comparison of Analog Clocks and Digital Clocks.

BACKGROUND: Time disorientation is one of the main symptoms observed in patients with dementia; however, their clock-reading ability has not been fully reported. OBJECTIVE: This study aimed to investigate the clock-reading ability of both digital and analog clocks in patients with dementia. We newly devised the clock-reading test (CRT) and the number-reading test (NRT) to assess cognitive factors that may affect clock-reading ability. Furthermore, the discriminating power of the CRT was calculated. METHODS: 104 participants were categorized based on their Mini-Mental State Examination (MMSE) scores as follows: subjective cognitive decline ∼ mild cognitive impairment (SCD∼MCI, N = 43), early Alzheimer's disease (AD) (N = 26), and middle-to-late AD (N = 35). Their cognitive abilities were evaluated using the clock-drawing test (CDT), CRT, and NRT. RESULTS: Cognitive decline leads to impairment of clock-reading ability which is more pronounced in the analog clocks than digital ones. This deficit in clock-reading is attributed to a loss of semantic memory regarding clocks at all stages. Additionally, visuospatial dysfunction and reduced ability of number recognition may lead to deficit in clock-reading in the advanced stage of AD. The discriminating power of the CRT (analog) (AUC = 0.853) was high enough to detect cognitive decline. CONCLUSION: Digital clocks are more readable by patients with dementia. Since reading clocks is closely associated with daily life, the CRT has proved to be a useful tool. A decline of analog clock-reading may be an early detector for the onset of dementia in elderly patients.

Perceptions and behaviours related to COVID-19 in patients with rheumatoid arthritis: a cross-sectional study.

OBJECTIVES: To study the perceptions and behavioural changes related to the coronavirus disease 2019 (COVID-19) in patients with rheumatoid arthritis (RA) and determine their associations with patient characteristics, such as health literacy. METHODS: This cross-sectional study was conducted from September to November of 2020 and included 400 outpatients with RA aged 18 and above. We measured self-reported perceptions as outcomes, such as awareness, knowledge and behaviours related to COVID-19. Health literacy and other characteristics as exposures were investigated using self-report questionnaires and electronic health records. To analyse the association between patient factors and the outcomes, multivariable linear and logistic regression models were performed. RESULTS: In total, 365 patients completed the survey. More than half (51%) of patients reported that they were 'very worried' about possible infection with COVID-19, whereas over 80% believed the possibility of getting COVID-19 was low. In the multivariable analyses, patients with low health literacy had limited knowledge about COVID-19 and did not change daily routines and perform preventive measures. CONCLUSIONS: In this pandemic, healthcare providers may need to be aware of more vulnerable individuals and share COVID-19 related information promptly and effectively with their patients. Key Points • This cross-sectional study aimed to investigate the perceptions and behavioural changes related to COVID-19 in patients with RA. • All patients were aware of COVID-19 and most of them worried about getting infected. • Health literacy, age, sex, disease activity and rheumatic drugs were associated with perceptions and behaviours related to COVID-19.

Dynamic theta/beta ratio of clinical EEG in Alzheimer's disease.

BACKGROUND: EEG of a resting state in Alzheimer disease (AD) patients and healthy controls (HC) are analyzed to identify the characteristics of EEG in AD. NEW METHOD: A dynamic box plot approach to the theta/beta ratio with various window durations is proposed to analyze EEG. RESULTS: Spectral results during a resting state in AD patients demonstrate the effect of relatively greater power in the low-frequency bands (i.e. 'slowing down' of the EEG). A significant difference is observed in the dynamic distribution of the theta/beta ratio in the AD and HC groups, which is related to the effect of 'slowing down'. There is a more obvious visual separation between the theta/beta ratio results for the AD and HC groups with increasing window durations. Variability of the theta/beta ratio can be observed with shorter window durations with a dynamic functional box plot. This provides a better classification accuracy by using the dynamic theta/beta ratio as a sensor to discriminate AD EEG from HC EEG by using the receiver operating characteristics (ROC) curve and the area under curve (AUC) with various window durations. COMPARISON WITH EXISTING METHOD(S): EEG spectral analysis and theta/beta ratio used to evaluate EEG typically rely on long time averaging. CONCLUSIONS: The dynamic box plot approach to the theta/beta ratio with various window durations provides the possibility of observing features of the EEG. The dynamic theta/beta ratio is a better sensor to discriminate AD EEG from HC EEG. Moreover, the reliability and accuracy of results can be increased by combining spectral analysis and the dynamic box plot approach to theta/beta ratio with various window durations.

Driving Performance and Its Correlation with Neuropsychological Tests in Senior Drivers with Cognitive Impairment in Japan.

BACKGROUND: With the rapid aging of the population, the issue of driving by dementia patients has been causing increasing concern worldwide. OBJECTIVE: To investigate the driving difficulties faced by senior drivers with cognitive impairment and identify the specific neuropsychological tests that can reflect specific domains of driving maneuvers. METHODS: Senior drivers with cognitive impairment were investigated. Neuropsychological tests and a questionnaire on demographic and driving characteristics were administered. Driving simulator tests were used to quantify participants' driving errors in various domains of driving. RESULTS: Of the 47 participants, 23 current drivers, though they had better cognitive functions than 24 retired drivers, were found to have impaired driving performance in the domains of Reaction, Starting and stopping, Signaling, and Overall (wayfinding and accidents). The parameters of Reaction were significantly related to the diagnosis, and the scores of MMSE, TMT-A, and TMT-B. As regards details of the driving errors, "Sudden braking" was associated with the scores of MMSE (ρ= -0.707, p < 0.01), BDT (ρ= -0.560, p < 0.05), and ADAS (ρ= 0.758, p < 0.01), "Forgetting to use turn signals" with the TMT-B score (ρ= 0.608, p < 0.05), "Centerline crossings" with the scores of MMSE (ρ= -0.582, p < 0.05) and ADAS (ρ= 0.538, p < 0.05), and "Going the wrong way" was correlated with the score of CDT (ρ= -0.624, p < 0.01). CONCLUSION: Different neuropsychological factors serve as predictors of different specific driving maneuvers segmented from driving performance.

Sex-specific differences in transcriptomic profiles and cellular characteristics of oligodendrocyte precursor cells.

The susceptibility to neurological and psychiatric disorders reveals sexual dimorphism in the structure and function of human brains. Recent evidence has also demonstrated the sex-related differences in cellular components of the brain, including neurons, microglia, astrocytes, and endothelial cells. Oligodendrocyte precursor cells (OPCs) regulate the neuronal system in various ways and play crucial roles in brain homeostasis beyond their well-known role as a reservoir for mature oligodendrocytes. Although recent studies have shown regional diversities and heterogeneities of OPCs, sex-related differences in OPCs are largely unknown. Here, we revealed transcriptomic differences in OPCs isolated from male and female neonatal rat brains. Furthermore, we demonstrated sex-dependent differences in OPCs regarding proliferation, migration, differentiation, tolerance against ischemic stress, energy metabolism, and the ability to regulate the blood-brain barrier integrity.

Factors associated with the job satisfaction of certified nurses and nurse specialists in cancer care in Japan: Analysis based on the Basic Plan to Promote Cancer Control Programs.

BACKGROUND: As the Japanese population ages, the number of cancer patients will likely increase. Therefore, qualified cancer health care providers should be recruited and retained. Nurse job satisfaction is influenced by numerous factors and may affect staff turnover and patient outcomes. OBJECTIVES: To evaluate the job satisfaction of certified nurses and nurse specialists in Japanese cancer care and elucidate factors associated with job satisfaction. METHODS: Participants in this cross-sectional study comprised 200 certified nurse specialists and 1,472 certified nurses working in Japanese cancer care. A chi-square test and logistic regression analysis were conducted to identify job satisfaction factors. RESULTS: Job satisfaction was present in 38.45% and 49.00% of certified nurses and nurse specialists, respectively. Certified nurses associated job satisfaction with cross-departmental activities (OR 2.24, p<0.001), positive evaluation from senior stuff (OR 4.58, p<0.001), appropriate staff allocation (OR 1.75, p<0.001), more than five years certified nurse experience (OR 1.91, p<0.001), and positive evaluation of the development of certified nurses (OR 2.13, p<0.01) and nurse specialists (OR 1.37, p<0.05). Low job satisfaction was associated with working on a ward (OR 0.51, p<0.001) and a capacity of more than 200 beds (OR 0.33, p = 0.00). Certified nurse specialists associated job satisfaction with palliative care team participation (OR 2.64, p<0.05), cross-sectional activities (OR 7.06, p<0.01), positive evaluation from senior stuff (OR 13.15, p<0.001), presence of certified nurses in radiation therapy (OR 2.91, p<0.05), positive certified nurse specialist development evaluation (OR 7.35, p<0.001), medical service fees (OR 3.78, p<0.01), and independent activities (OR 11.34, p<0.01). CONCLUSIONS: We identified factors related to activities, facilities, and the cancer care team associated with job satisfaction of certified nurses and nurse specialists in Japanese cancer care. Suggestions are provided to enhance job satisfaction through Japan's Basic Plan to Promote Cancer Control, which may help hospital administrators retain nursing staff.

Synaptic Vesicle Protein 2B Negatively Regulates the Amyloidogenic Processing of AßPP as a Novel Interaction Partner of BACE1.

BACKGROUND: Given that amyloid-ß (Aß) peptide is produced and released at synapses, synaptic Aß is one of the promising therapeutic targets to prevent synaptic dysfunction in Alzheimer's disease (AD). Although Aß production begins with the cleavage of the amyloid-ß protein precursor (AßPP) by ß-site AßPP cleaving enzyme 1 (BACE1), the mechanism on how BACE1 is involved in AßPP processing at synapses remains unclear. OBJECTIVE: This study aimed to identify novel BACE1 interacting proteins regulating Aß production at the synapse. METHODS: BACE1 interacting proteins were pulled down using a mass spectrometry-based proteomics of wild-type (WT) rat brain synaptoneurosome lysates utilizing anti-BACE1 antibody. Then, a novel BACE1 interactor was identified and characterized using experimental systems that utilized transfected cells and knockout (KO) mice. RESULTS: Synaptic vesicle protein 2B (SV2B) was identified as a novel presynaptic interaction partner of BACE1. In HEK293 cells, co-overexpression of SV2B with BACE1 significantly reduced the sAßPPß and Aß levels released in the media; thus, SV2B overexpression negatively affected the AßPP cleavage by BACE1. Compared with those of WT mice, the hippocampal lysates of SV2B knockout mice had significantly elevated Aß levels, whereas the ß-secretase activity and the AßPP and BACE1 protein levels remained unchanged. Finally, a fractionation assay revealed that BACE1 was mislocalized in SV2B KO mice; hence, SV2B may be involved in BACE1 trafficking downregulating the amyloidogenic pathway of AßPP. CONCLUSION: SV2B has a novel role of negatively regulating the amyloidogenic processing of AßPP at the presynapses.

Nurses' Perception of the Bed Alarm System in Acute-Care Hospitals.

INTRODUCTION: In hospitals, the nurse uses the bed alarm system for patients' safety, which may have some forms of physical restraints included, depending on the situation. However, the nurses' perceptions of the bed alarm system with reference to restraints are yet to be clarified. Moreover, there were no reports that can shed light upon the factors that relate to nurses' perceptions about the bed alarm system in Japan. The objective of this study is to investigate the nurses' perception on whether the bed alarm can be considered as a form of physical restraint and to elucidate the factors that pertain to the nurses' perceptions regarding the bed alarm. METHODS: This study conducted a quantitative cross-sectional survey. We used bivariate logistic regression analyses to investigate the nurses' perception and the factors affecting these perception. Ethical approval was obtained from the research ethics committee of the Kyoto University. Participants opted for answering the questionnaire voluntarily. RESULTS: The sample population comprised of 289 nurses from 10 acute-care hospitals. Out of these, 214 (74.0%) nurses considered the bed alarm system as a form of restraint, and 75 nurses (26.0%) did not. Furthermore, the nurses' perception was relevant to the hospitals that they belonged to, their years of experience, and the content of education. It was especially interesting that the group of nurses with little experience had the consciousness of being considered the bed alarm as restraint compared with nurses with many years of experience. CONCLUSION: The alarm systems are gradually being considered to be classified as a restraint. Hospitals should ensure providing an ethically sensitive climate and appropriate educational opportunities to help nurses build these perceptions for patient care. An ethically sensitive climate and appropriate educational opportunities would lead to an environment that nurtures nurses with the ability to recognize problems in daily care.

Two-Point Dynamic Observation of Alzheimer's Disease Cerebrospinal Fluid Biomarkers in Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND: Extensive research into cerebrospinal fluid (CSF) biomarkers was performed in patients with idiopathic normal pressure hydrocephalus (iNPH). Most prior research into CSF biomarkers has been one-point observation. OBJECTIVE: To investigate dynamic changes in CSF biomarkers during routine tap test in iNPH patients. METHODS: We analyzed CSF concentrations of tau, amyloid-ß (Aß) 42 and 40, and leucine rich α-2-glycoprotein (LRG) in 88 consecutive potential iNPH patients who received a tap test. We collected two-point lumbar CSF separately at the first 1 ml (First Drip (FD)) and at the last 1 ml (Last Drip (LD)) during the tap test and 9 patients who went on to receive ventriculo-peritoneal shunt surgery each provided 1 ml of ventricular CSF (VCSF). RESULTS: Tau concentrations were significantly elevated in LD and VCSF compared to FD (LD/FD = 1.22, p = 0.003, VCSF/FD = 2.76, p = 0.02). Conversely, Aß42 (LD/FD = 0.80, p < 0.001, VCSF/FD = 0.38, p = 0.03) and LRG (LD/FD = 0.74, p < 0.001, VCSF/FD = 0.09, p = 0.002) concentrations were significantly reduced in LD and VCSF compared to FD. Gait responses to the tap test and changes in cognitive function in response to shunt were closely associated with LD concentrations of tau (p = 0.02) and LRG (p = 0.04), respectively. CONCLUSIONS: Dynamic changes were different among the measured CSF biomarkers, suggesting that LD of CSF as sampled during the tap test reflects an aspect of VCSF contributing to the pathophysiology of iNPH and could be used to predict shunt effectiveness.

Idea density in Japanese for the early detection of dementia based on narrative speech.

BACKGROUND: Idea density (ID), a natural language processing-based index, was developed to aid in the detection of dementia through the analysis of English narratives. However, it has not been applied to non-English languages due to the difficulties in translating grammatical concepts. In this study, we defined rules to count ideas in Japanese narratives based on a previous study and proposed a novel method to estimate ID in Japanese text using machine translation. MATERIALS: The study participants comprised 42 Japanese patients with dementia aged 69-98 years (mean: 84.95 years). We collected free narratives from the participants to build a speech corpus. The narratives of the patients were translated into English using three machine translation systems: Google Translate, Bing Translator, and Excite Translator. The ID in the translated text was then calculated using the Dependency-based Propositional ID (DEPID), an English ID scoring tool. RESULTS: The maximum correlation coefficient between ID calculated using DEPID-R-ADD (a modified DEPID method to calculate ID after removing vague sentences) and the Mini-Mental State Examination score was 0.473, indicating a moderate correlation. DISCUSSION: The results demonstrate the feasibility of machine translation-based ID measurement. We believe that the basic concept of this translation approach can be applied to other non-English languages.

Fibronectin type III domain-containing protein 5 interacts with APP and decreases amyloid ß production in Alzheimer's disease.

The deposition of Amyloid-beta peptides (Aß) is detected at an earlier stage in Alzheimer's disease (AD) pathology. Thus, the approach toward Aß metabolism is considered to play a critical role in the onset and progression of AD. Mounting evidence suggests that lifestyle-related diseases are closely associated with AD, and exercise is especially linked to the prevention and the delayed progression of AD. We previously showed that exercise is more effective than diet control against Aß pathology and cognitive deficit in AD mice fed a high-fat diet; however, the underlying molecular mechanisms remain poorly understood. On the other hand, a report suggested that exercise induced expression of fibronectin type III domain-containing protein 5 (FNDC5) in the hippocampus of mice through PGC1α pathway. Thus, in the current study, we investigated a possibility that FNDC5 interacts with amyloid precursor protein (APP) and affects Aß metabolism. As a result, for the first time ever, we found the interaction between FNDC5 and APP, and forced expression of FNDC5 significantly decreased levels of both Aß40 and Aß42 secreted in the media. Taken together, our results indicate that FNDC5 significantly affects ß-cleavage of APP via the interaction with APP, finally regulating Aß levels. A deeper understanding of the mechanisms by which the interaction between APP and FNDC5 may affect Aß production in an exercise-dependent manner would provide new preventive strategies against the development of AD.

Degradation of amyloid ß peptide by neprilysin expressed from Borna disease virus vector.

Accumulation of amyloid ß (Aß40 and Aß42) in the brain is a characteristic of Alzheimer's disease (AD). Because neprilysin (NEP) is a major Aß-degrading enzyme, NEP delivery in the brain is a promising gene therapy for AD. Borna disease virus (BoDV) vector enables long-term transduction of foreign genes in the central nerve system. Here, we evaluated the proteolytic ability of NEP transduced by the BoDV vector and found that the amounts of Aß40 and Aß42 significantly decreased, which suggests that NEP expressed from the BoDV vector is functional to degrade Aß.