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Alzheimer's disease is the most common dementia disease and the main cause of death. The hallmark is neurofibrillary tangles (abnormal aggregates of tau protein) and beta-amyloid (Aβ) neuritic plaques that leads to impaired cognitive function such as memory loss and learning difficulties. Researchers have discovered that intermittent fasting improves these cognitive abilities, even though eating regularly is recommended for good cognition. This systematic review aims to investigate further if intermittent fasting improves cognitive function in Alzheimer’s disease and if levels of Aβ and tau pathology explain these changes in cognitive function. The research question is: does intermittent fasting improve cognitive abilities in Alzheimer’s disease and does the levels of Aβ and tau pathology explain these cognitive changes? A literature search for articles was performed on three electronic databases: Pubmed, Web of Science, and WorldCat which gave n=744 articles. The cognitive tests showed a trend toward improved memory, learning, and exploratory behavior in Alzheimer’s disease from intermittent fasting. However, the effects on the levels of Aβ and tau pathology were inconsistent, which invites the possibility of a more prominent, underlying issue of Alzheimer's disease.

Sammanfattning   Bakgrund: Övervikt och fetma har blivit en hälsofarlig nödsituation i västvärlden, i synnerhet bukfetma som är en av de viktigaste riskfaktorerna för kardiovaskulära sjukdomar. Den västerländska dieten domineras av högt förädlade livsmedel till låg kostnad vilket snabbt har utvecklat övervikt och överviktsrelaterade sjukdomar. Det finns olika behandlingsmetoder för att minska övervikt och fetma, där kost är en viktig komponent. Lågkolhydratkost kommer alltmer i fokus, som ett alternativ till de rådande näringsrekommendationerna. För att stödja och motivera personer med övervikt och fetma kan sjuksköterskan förmedla en personcentrerad egenvård enligt Orem. Sjuksköterskan skall enligt lag arbeta evidensbaserat och det krävs ständig uppdatering av forskningsläget. Syfte: Syftet var att studera effekten av lågkolhydratkost hos personer med övervikt och fetma. Metod: Litteraturöversikten är av kvantitativ metod och innehåller 15 vetenskapliga artiklar. Analysmodellen som användes var Fribergs analys. Resultat: Effekter av lågkolhydratkost visar signifikanta förbättringar i framförallt viktnedgång men även i blodtryck, blodfetter och blodsocker. De största effekterna av de olika variablerna sågs efter sex månader. Dessa effekter gav ofta en minskad användning av antidiabetika som följd. Slutsats: Då lågkolhydratkost har gynnsamma effekter på viktnedgång, blodfetter och blodsocker är behovet stort av långtidsstudier. Sjuksköterskan har en viktig roll att stödja och motivera personer med övervikt och fetma till livsstilsförändringar. Nyckelord: Viktnedgång, ketogen kost, lågkolhydratkost, egenvård / Summary Low-carbohydrate diets for overweight and obesity - A literature review   Background: Overweight and obesity has become a health hazard emergency in the western world, especially abdominal obesity which is one of the major risk factors for cardiovascular diseases. The Western diet is dominated by highly processed food at low cost, which has rapidly developed obesity and obesity related diseases. There are various treatment methods to reduce overweight and obesity by diet which is an important component. Low-carbohydrate diet comes increasingly into focus, as an alternative to the current nutritional recommendations. To support and motivate people with overweight and obesity, the nurse can convey a person-centered self-care according to Orem. The nurse should, by law, set their work based on evidence and that requires a continuous update of available research. Objective: The objective was to study the effect of low-carbohydrate diet in people with overweight and obesity. Method: The literature review is the quantitative method and contains 15 scientific articles. The analysis model used was Friberg analysis. an important role to support and motivate people with overweight Result: Effects of low-carbohydrate show significant improvements especially in weight loss but also in blood pressure, blood fats and blood sugar. The main effects of the different variables were observed after six months. These effects often gave a reduced use of antidiabetic drugs as a result. Conclusion: Since low-carbohydrate proven to have beneficial effects on weight loss, blood fat and blood sugar there is a great need for long-term studies. The nurse has and obesity to lifestyle changes. Keywords: Weight loss, ketogenic diet, low-carbohydrate diet, self-care

Introdução: a epilepsia é uma doença neurológica, cuja prevalência é de 0,5 a 1% na população, sendo que 20 a 30% dos pacientes apresentam crises refratárias ao tratamento medicamentoso. A dieta cetogênica (DC) composta por alto teor de gorduras, baixo teor de carboidratos e quantidade proteica adequada tem emergido como um tratamento adjuvante e eficaz no controle de crises. Apesar de sua eficácia ser bem descrita na literatura, em humanos pouco se sabe sobre influência da DC em marcadores oxidativos e na modulação de fatores de transcrição como o NF-kB e Nrf2. Além disso, não se sabe sobre o impacto que diferentes tipos de ácidos graxos dietéticos ofertados na DC poderiam ocasionar nesses marcadores. Objetivo: avaliar o impacto da modificação do perfil de ácidos graxos dietéticos ofertados na DC SAFA sobre o perfil lipídico, oxidativo e ativação de fatores de transcrição NF-kB e Nrf2 em crianças e adolescentes com epilepsia refratária submetidos ao tratamento com dieta cetogênica. Metodologia: tratase de um ensaio clínico com seguimento de 6 meses, no qual o grupo DC SAFA recebeu uma dieta rica em colesterol e gordura saturada, e o grupo DC NSAFA recebeu uma dieta com redução de pelo menos 20% de gorduras saturadas; aumento em > 50% da oferta de ácido graxo monoinsaturados e ácidos graxos poli-insaturados quando comparados ao grupo DC SAFA. Foram avaliadas características socioeconômicas e clínicas e marcadores: antropométricos; bioquímicos de adesão a dieta; de consumo alimentar; de estresse oxidativo; e de capacidade antioxidante em ambos os grupos. Esses parâmetros foram avaliados em três momentos: antes do início da DC (T0), três meses (T1) e seis meses (T2) após o início do tratamento. As análises estatísticas foram realizadas através do software SPSS. Resultados: Foram incluídas 26 crianças e adolescentes no grupo DC clássica e 26 no grupo DC modificada. A DC NSAFA conferiu alterações menos intensas no perfil lipídico com menor percentual de aumento de colesterol total, LDL-C, APO B, razão LDL-C por HDL-C, razão HDL-C por APO A, razão LDL-C por APO B, colesterol não HDL e ácidos graxos não esterificados em comparação com a DC SAFA. Em ambas as dietas houve aumento significativo da concentração de LDLox. Foi observado o aumento significativo do NFkB na DC SAFA, sem diferenças significativas no percentual de mudança dessa variável entre as intervenções, além disso na DC SAFA houve redução de Nrf2 e o mesmo se comportou de forma distinta entre as intervenções, sendo que na DC SAFA houve redução significativa desse marcador. Conclusão: a DC SAFA demonstrou apresentar pior perfil de resposta lipídica, inflamatória e oxidante em comparação a DC NSAFA, a adoção da DC NSAFA para o tratamento da epilepsia refratária poderia minimizar os efeitos negativos observados na DC SAFA e atenuar o principal efeito adverso observado que são as dislipidemias. / Introduction: epilepsy is a neurological disease, its prevalence is estimated about 0,5 to 1 % in the population and 20 to 30% are refractory to the drug treatment. The ketogenic diet (KD) composed by high content of fat, low quantity of carbohydrate and adequate content of protein it is an adjuvant treatment with high efficacy in seizure control. Although it is well known about the efficacy of the diet, in humans there are few studies about the influence of the diet in oxidative biomarkers and its modulation in transcription factors such as NF-kB and Nrf2. Moreover it is not known about the impact of different types of dietetic fatty acids offers in KD could be influence in oxidative biomarkers and transcription factors. Objective: to evaluate and compare the impact of two different ketogenic diet, one composed by high content of saturated fatty acids (KD SAFA) and another one composed by high content of monounsaturated fatty acids and polyunsaturated fatty acids (KD NSAFA), on lipid and oxidative profile and activations of NF-kB and Nrf2 transcriptions factors in children and adolescents with refractory epilepsy on dietetic treatment with KD. Methods: clinical study, with 6 months of follow up, the patients was divided in two groups: one received a KD rich in saturated fatty acids and cholesterol (KD SAFA) and other received a KD with 20% less content of saturated fatty acids, increase in 50% of monounsaturated and polyunsaturated fatty acids comparing to KD SAFA (KD NSAFA). It was evaluated socioeconomic and clinical characteristics, anthropometric measure, food intake and lipids, oxidative and inflammatory biomarkers. The patients was evaluated in three different moments: before start the diet (T0), three months after start the KD (T1) and six months after start the KD (T2). The statistical analysis was performed using the software SPSS. Results: It was included 26 children and adolescents in KD SAFA and 26 in KD NSAFA. The participants treated with KD NSAFA had less modifications on classical lipid profile with less increase of: total cholesterol, LDL-C, APO B, LDL-C/HDL-C, HDL-C/APO A, LDL-C/APO B, non HDL cholesterol and non esterified fatty acids comparing to the participants treated with KD SAFA. In both diets there was a significant increase in oxidized LDL. It was observed increase of NFkB in the group treated with KD SAFA, without differences on the percentage of change of this biomarker between the interventions, in addition on the KD SAFA there was decrease in Nrf2 and the percentage of change it was different between the interventions with more reduction of this biomarker on KD SAFA. Conclusion: the KD SAFA showed worst profile in lipid, oxidative and inflammatory parameters comparing to KD NSAFA, suggesting that the use of KD NSAFA could be attenuate one of the main negative effect that are dyslipidemias.

Thesis advisor: Thomas N. Seyfried / Epilepsy is a prevalent disabling chronic and socially isolating neurological disorder that involves recurrent abnormal discharges of neurons. Despite seizures afflicting about 10% of people worldwide, antiepileptic drugs (AEDs) are largely unable to manage seizures in many persons with epilepsy. As an alternative to AEDs, dietary therapies possess a broad therapeutic potential in both humans and animals models of various neurological and neurodegenerative disease etiologies. My research focus was to identify the therapeutic efficacy and potential mechanism(s) of action of calorie restriction (CR) and the ketogenic diet (KD) in both the epileptic EL mouse model and the Mecp2<super>308/y<super/> mouse model of Rett syndrome. My findings indicate that both the KD and CR can reduce seizure susceptibility in EL mice, a natural model for multifactorial idiopathic generalized epilepsy. CR and circulating glucose and ketone levels significantly influence the therapeutic efficacy of the KD. A concurrent reduction in circulating plasma glucose levels and elevation in circulating plasma &beta-hydroxybutyrate levels was predicted to associate with the anticonvulsant effect of these diets in EL mice. For the first time, I was able to show that a KD fed in unrestricted amount is able to reduce seizure threshold in EL mice. Interestingly, supplementation of calories in the form of carbohydrate in the water of calorie-restricted EL mice results in a diminished anticonvulsant efficacy of the KD. In my effort to elucidate the neuroprotective mechanism(s) associated with these changes in metabolite availability, I started investigating the complex alterations occurring in multiple integrated neural and metabolic processes. Furthermore, I showed that a restricted KD diet improves aspects of the behavioral abnormalities seen in Rett mice, in particular with respect to anxiety. Finally, for the first time, I provide a standardized protocol for the implementation of diet therapies in the management of an array of neurological and neurodegenerative diseases, which ultimately may help elucidate the complex neuroprotective mechanism(s) of CR and the KD. This research overall has provided a new understanding in the therapeutic efficacy of diets in epilepsy and Rett Syndrome. / Thesis (PhD) — Boston College, 2010. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.

Introdução: a epilepsia é uma doença neurológica, cuja prevalência é de 0,5 a 1% na população, sendo que 20 a 30% dos pacientes apresentam crises refratárias ao tratamento medicamentoso. A dieta cetogênica (DC) composta por alto teor de gorduras, baixo teor de carboidratos e quantidade proteica adequada tem emergido como um tratamento adjuvante e eficaz no controle de crises. Apesar de sua eficácia ser bem descrita na literatura, em humanos pouco se sabe sobre influência da DC em marcadores oxidativos e na modulação de fatores de transcrição como o NF-kB e Nrf2. Além disso, não se sabe sobre o impacto que diferentes tipos de ácidos graxos dietéticos ofertados na DC poderiam ocasionar nesses marcadores. Objetivo: avaliar o impacto da modificação do perfil de ácidos graxos dietéticos ofertados na DC SAFA sobre o perfil lipídico, oxidativo e ativação de fatores de transcrição NF-kB e Nrf2 em crianças e adolescentes com epilepsia refratária submetidos ao tratamento com dieta cetogênica. Metodologia: tratase de um ensaio clínico com seguimento de 6 meses, no qual o grupo DC SAFA recebeu uma dieta rica em colesterol e gordura saturada, e o grupo DC NSAFA recebeu uma dieta com redução de pelo menos 20% de gorduras saturadas; aumento em > 50% da oferta de ácido graxo monoinsaturados e ácidos graxos poli-insaturados quando comparados ao grupo DC SAFA. Foram avaliadas características socioeconômicas e clínicas e marcadores: antropométricos; bioquímicos de adesão a dieta; de consumo alimentar; de estresse oxidativo; e de capacidade antioxidante em ambos os grupos. Esses parâmetros foram avaliados em três momentos: antes do início da DC (T0), três meses (T1) e seis meses (T2) após o início do tratamento. As análises estatísticas foram realizadas através do software SPSS. Resultados: Foram incluídas 26 crianças e adolescentes no grupo DC clássica e 26 no grupo DC modificada. A DC NSAFA conferiu alterações menos intensas no perfil lipídico com menor percentual de aumento de colesterol total, LDL-C, APO B, razão LDL-C por HDL-C, razão HDL-C por APO A, razão LDL-C por APO B, colesterol não HDL e ácidos graxos não esterificados em comparação com a DC SAFA. Em ambas as dietas houve aumento significativo da concentração de LDLox. Foi observado o aumento significativo do NFkB na DC SAFA, sem diferenças significativas no percentual de mudança dessa variável entre as intervenções, além disso na DC SAFA houve redução de Nrf2 e o mesmo se comportou de forma distinta entre as intervenções, sendo que na DC SAFA houve redução significativa desse marcador. Conclusão: a DC SAFA demonstrou apresentar pior perfil de resposta lipídica, inflamatória e oxidante em comparação a DC NSAFA, a adoção da DC NSAFA para o tratamento da epilepsia refratária poderia minimizar os efeitos negativos observados na DC SAFA e atenuar o principal efeito adverso observado que são as dislipidemias. / Introduction: epilepsy is a neurological disease, its prevalence is estimated about 0,5 to 1 % in the population and 20 to 30% are refractory to the drug treatment. The ketogenic diet (KD) composed by high content of fat, low quantity of carbohydrate and adequate content of protein it is an adjuvant treatment with high efficacy in seizure control. Although it is well known about the efficacy of the diet, in humans there are few studies about the influence of the diet in oxidative biomarkers and its modulation in transcription factors such as NF-kB and Nrf2. Moreover it is not known about the impact of different types of dietetic fatty acids offers in KD could be influence in oxidative biomarkers and transcription factors. Objective: to evaluate and compare the impact of two different ketogenic diet, one composed by high content of saturated fatty acids (KD SAFA) and another one composed by high content of monounsaturated fatty acids and polyunsaturated fatty acids (KD NSAFA), on lipid and oxidative profile and activations of NF-kB and Nrf2 transcriptions factors in children and adolescents with refractory epilepsy on dietetic treatment with KD. Methods: clinical study, with 6 months of follow up, the patients was divided in two groups: one received a KD rich in saturated fatty acids and cholesterol (KD SAFA) and other received a KD with 20% less content of saturated fatty acids, increase in 50% of monounsaturated and polyunsaturated fatty acids comparing to KD SAFA (KD NSAFA). It was evaluated socioeconomic and clinical characteristics, anthropometric measure, food intake and lipids, oxidative and inflammatory biomarkers. The patients was evaluated in three different moments: before start the diet (T0), three months after start the KD (T1) and six months after start the KD (T2). The statistical analysis was performed using the software SPSS. Results: It was included 26 children and adolescents in KD SAFA and 26 in KD NSAFA. The participants treated with KD NSAFA had less modifications on classical lipid profile with less increase of: total cholesterol, LDL-C, APO B, LDL-C/HDL-C, HDL-C/APO A, LDL-C/APO B, non HDL cholesterol and non esterified fatty acids comparing to the participants treated with KD SAFA. In both diets there was a significant increase in oxidized LDL. It was observed increase of NFkB in the group treated with KD SAFA, without differences on the percentage of change of this biomarker between the interventions, in addition on the KD SAFA there was decrease in Nrf2 and the percentage of change it was different between the interventions with more reduction of this biomarker on KD SAFA. Conclusion: the KD SAFA showed worst profile in lipid, oxidative and inflammatory parameters comparing to KD NSAFA, suggesting that the use of KD NSAFA could be attenuate one of the main negative effect that are dyslipidemias.

A dieta cetogênica (DC) é um tratamento não farmacológico prescrito especialmente para crianças e adolescentes com epilepsia refratária. A composição da dieta cetogênica é baseada no alto teor de gorduras, baixo teor de carboidratos e teor proteico moderado, sendo a produção de corpos cetônicos o mecanismo provável envolvido no controle das crises epilépticas. Apesar dos benefícios clínicos, a relação entre DC e o risco cardiometabólico não está bem estabelecida, especialmente sob os fatores de risco não clássicos. Objetivo: comparar os efeitos da dieta cetogênica clássica com a dieta cetogênica modificada nas subfrações de LDL e HDL, nos marcadores oxidativos, no perfil de apolipoproteinas e no perfil lipídico de crianças e adolescentes com epilepsia refratária, além do efeito clínico no controle da epilepsia. Métodos: Estudo de intervenção com recrutamento de crianças e adolescentes com epilepsia refratária de 1 a 19 anos de ambos os sexos do Instituto da Criança do Hospital das Clínicas da FMUSP. O grupo controle recebeu DC clássica e o grupo caso recebeu a DC modificada com redução em pelo menos 20% de ácidos graxos saturados (AGS) e redução da relação w6/w3 em pelo menos 50% em comparação a DC clássica. Para ambos os grupos foram analisados os seguintes parâmetros bioquímicos no período basal, após 3 meses e 6 meses de DC: perfil lipídico clássico, concentração de ácidos graxos não esterificados (AGNEs), substâncias reativas ao ácido tiobarbitúrico (TBARs), subfrações de lipoproteina de baixa densidade (LDL) e lipoproteína de alta densidade (HDL), e perfil de apolipoproteínas (APOA-I e APOB). Além da avaliação clínica, antropométrica e de consumo alimentar. Resultados: A redução de crises e dos fármacos antiepilépticos foi semelhante entre os grupos. O aumento na concentração de colesterol total (CT) e LDL foi inferior no grupo caso, a Não-HDL manteve-se significativamente menor no grupo caso em comparação ao grupo controle e a relação LDL/APOB foi superior no grupo controle após 6 meses de DC. O percentual de partículas pequenas de LDL apresentou aumento superior em 208% no grupo controle comparado ao grupo caso, e consequentemente o tamanho de LDL apresentou maior redução no grupo controle. A incidência de dislipidemia foi significativamente inferior no grupo caso considerando os pontos de corte para LDL (>=130 mg/dL) e não-HDL (>=145 mg/dL). Não houve diferença entre os grupos na concentração de ácidos graxos não esterificados (AGNES) e substâncias reativas ao ácido tiobarbitúrico (TBARs). Conclusão: A mudança do perfil de gorduras 10 contribuiu para melhora das concentrações de marcadores de risco cardiometabólico (CT, LDL e LDL pequenas) e consequentemente, perfil mais cardioprotetor nos pacientes do grupo caso. / The ketogenic diet (KD) is a non-pharmacological treatment especially prescribed to children and adolescentes with refractory epilepsy. The composition of the ketogenic diet is based on the high fat, low carbohydrate and moderate protein. The production of ketone bodies is the probable mechanism involved in the control of epileptic seizures. Despite the clinical benefits, the relationship between KD and cardiometabolic risk is not well established, especially under non-classical risk factors. Objective: to compare the effects of the classical KD with the modified KD on the LDL and HDL subfractions, in oxidative biomarkers, in apolipoprotein profile and lipid profile of children and adolescentes with refractory epilepsy, as well as the clinical effect on control of seizure. Methods: Dietary intervention study with recruitment of children and adolescentes with refractory epilepsy aged 1 to 19 years of both sexes from the Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da USP. The control group received classical KD and the case group received modified KD with a reduction of at least 20% saturated fatty acids (SFA) and a reduction of the w6/w3 ratio by at least 50% compared to classic KD. For both groups, the following biochemical parameters were analyzed at baseline and after 3 and 6 months of the KD: classical lipid profile, concentration of non-esterified fatty acids (NEFAs), thiobarbituric acid reactive substances (TBARs), low density lipoprotein (LDL) and high density lipoprotein (HDL) subfractions, size LDL, and apolipoprotein profile (APOA-I and APOB). In addition to clinical, anthropometric and food consumption assessment. Results: The reduction of seizures and antiepileptic drugs was similar between the groups. The increase in total cholesterol (TC) and LDL levels was lower in the case group, non-HDL remained significantly lower in the case group compared to the control group and the LDL/APOB ratio was higher in the control group after 6 months of KD. The percentage of small LDL particles showed a 208% higher in the control group than case group. Consequently, the LDL size showed a greater reduction in the control group. The incidence of dyslipidemia was significantly lower in the case group considering cut-off points for LDL (>=130 mg/dL) and non-HDL (>=145 mg/dL). There was no difference between the groups in the NEFAs and TBARs levels. Conclusion: The change in the fatty acids profile contributed to improvement the concentrations of cardiometabolic risk markers (TC, 12 LDL and small LDL), and consequently, a more cardioprotective profile in the patients of case group.

Compte tenu de l'absence de traitement pharmacologique efficace contre la maladie d'Alzheimer (MA), le développement d'approches thérapeutiques alternatives telles que le régime cétogène (« ketogenic diet » : KD) pourrait être envisagé. Le KD est un régime riche en graisses, basé sur la production de corps cétoniques (« ketone nodies » : KB) dans le sang. En raison des effets bénéfiques du KD sur le système nerveux central et de l'absence de données publiées sur la barrière hémato-encéphalique (BHE), nous avons utilisé une approche in vivo / in vitro pour étudier l'effet du KD et des KB sur la BHE. Pour l'étude in vivo, le sang de souris 129Sv a été récolté afin d’effectuer le dosage du beta-hydroxybutyrate et du glucose. Les capillaires cérébraux ont été isolés de cortex des souris, et des RT-qPCR ont été effectuées pour évaluer l'expression de l'ARNm des transporteurs / récepteurs impliqués dans la synthèse et le transport de KB, de glucose et du peptide bêta amyloïde. Les analyses transcriptionnelles ont été réalisées également dans un modèle in vitro de BHE, composé de cellules endothéliales dérivées de cellules souches hématopoïétiques (BLECs) en état de cétose. Après confirmation de l'intégrité des jonctions cellulaires des BLECs, Enfin, des expériences de transport de peptides beta amyloïde fluorescents après traitement avec les KBs ont été réalisées in vitro. Nos résultats montrent que les KBs modulent la physiologie de la BBB et l'expression de certains transporteurs et récepteurs du peptide bêta amyloïde, renforcent ainsi notre motivation à décrypter les mécanismes moléculaires et cellulaires au niveau vasculaire et plus précisément au niveau de la BHE. / Given the current absence of an effective pharmacologic treatment for Alzheimer’s disease (AD), the development of alternative therapeutic approaches (such as the ketogenic diet, KD) might be considered. The KD is a low-carbohydrate, high-fat diet based on the production of ketone bodies (KBs) in the blood. In view of the KD’s beneficial effects on the central nervous system and the lack of published data on the blood brain barrier (BBB), we used an in vivo/in vitro approach to investigate the effect of the KD and KBs on the BBB. For the in vivo study, blood from 129Sv mice was assayed for beta-hydroxybutyrate and glucose dosage. Brain capillaries were isolated from mouse cortices, and RT-qPCR assays were used to evaluate the mRNA expression of transporters/receptors involved in the synthesis and transport of KBs, glucose and beta-amyloid peptide. The mRNA assays were also performed in an in vitro BBB model, based on brain-like endothelial cells (BLECs). After a ketotic state had been established and the BLECs’ integrity had been confirmed, we evaluated the mRNA expression of KB-, glucose- and amyloid-beta-related genes. Lastly, the transport of fluorescently labelled beta-amyloid peptide across the BBB was studied after treatment with KBs. Our results showed that KBs modulate the physiology of the BBB by regulating the expression of certain beta-amyloid peptide transporters/receptors and amyloid peptide-synthesizing enzymes. These data suggest that it is possible to modulate key molecular players in beta-amyloid peptide transport and synthesis at the BBB, and thus open up new perspectives for studying KB-related therapeutic approaches.