Applying network theory to bat roosts to assess the impact of human-induced environmental stre

Tese de mestrado, Ecologia e Gestão Ambiental, Universidade de Lisboa, Faculdade de CiênciasApesar dos custos energéticos associados a longas deslocações, várias espécies animais dependem de áreas espacialmente distantes para completar os seus ciclos de vida. Estes movimentos podem englobar grandes áreas, porém o espaço útil e intensamente utilizado é, em geral, muito mais reduzido. O conjunto das áreas intensamente utilizadas, a hierarquia de importância e as deslocações entre elas são importantes para o estudo da ecologia, comportamento e conservação destas espécies animais. Dado o seu meio de locomoção, as espécies voadoras em geral conseguem percorrer maiores distâncias que as espécies terrestres. Várias espécies de morcegos efetuam múltiplas deslocações anuais para completar o seu ciclo de vida. O seu uso de abrigos, apesar de filopátrico, permite-lhes visitar outros abrigos em diferentes fases de vida. Este comportamento e a sobreposição de áreas vitais das colónias contribuem para a manutenção da estrutura genética das espécies. As espécies de morcegos cavernícolas enfrentam limitações associadas à reduzida disponibilidade de abrigos (minas e grutas) e à qualidade do habitat circundante aos mesmos, que tem de satisfazer as suas necessidades de dieta e de disponibilidade de água. Consequentemente, as ameaças à conservação dos morcegos cavernícolas, como a intensificação de uso de solo, poluição e fogos, vão ter um maior impacto quando ocorrerem próximo dos seus abrigos. Para analisar áreas de uso espacial com padrões de movimento complexos é benéfico ter ferramentas que simplifiquem as análises. A aplicação de técnicas de análise de redes nestes sistemas complexos possibilita a sua compreensão integrada permitindo ainda criar modelos-padrão. Os objetivos principais deste trabalho são (i) a criação de uma rede espacial de abrigos de morcegos; (ii) caracterização do tipo de rede e identificação da importância de cada vértice (abrigo); e (iii) análise do potencial impacto de dois fatores ambientais (fogos florestais e alteração do uso do solo) nos (iii.a) abrigos mais importantes (HRR), e (iii.b) na conectividade da rede. Com recurso à base de dados do Programa de Anilhagem de Morcegos que apresenta 70 090 registos obtidos ao longo de 33 anos, criámos um modelo da rede de movimentos de morcegos. Foram digitalizados os registos dos últimos 14 anos e detetados e eliminados erros em toda a base de dados. Como modelo utilizou-se a espécie Miniopterus schreibersii (Kuhl 1817) dado a elevada percentagem de entradas na base de dados (>85%) e as suas características ecológicas. Para a criação do modelo da rede espacial (“MiniS”) utilizaram-se os abrigos como vértices e os movimentos de morcegos entre abrigos como as arestas que os conectam, bem como as respetivas coordenadas. Para avaliar a estrutura da rede foram calculadas métricas de centralidade - grau e “betweenness” - de conectividade - “bridgeness” - e de aglomeração - estrutura de modularidade otimizada, coeficiente de agrupamento e modularidade. A classificação da estrutura da rede foi feita com recurso ao enquadramento da distribuição do grau. Adicionalmente, calculamos métricas de centralidade e conectividade para criar uma lista ordenada dos abrigos mais importantes (HRR - “high ranking roosts”). Testámos a sensibilidade da rede MiniS ao impacto de fatores naturais usando simulações de remoção de abrigos. A ordem de remoção foi baseada nos registos históricos de cada abrigo em relação a dois fatores, fogos florestais e de usos do solo (artificial, agricultura e floresta). Os resultados das simulações foram comparados com valores máximos de impacto, simulados com a remoção de abrigos por ordem das métricas de grau e “betweenness” e valores mínimos de impacto, simulados com a remoção de abrigos por ordem aleatória. Calculámos também as perdas de conectividade associadas às métricas de centralidade “hub” e "authority". Para compreender a influência da distância ao abrigo repetimos as análises para os fatores ambientais - incêndios e uso do solo - nos raios de 1, 2, 5 e 10 km ao redor do abrigo. Analisámos também o impacto de cada fator a nível dos HRR. A rede de abrigos MiniS apresenta 99 vértices conectados por 275 arestas (inclui 1 vértice isolado). A distribuição de abrigos subterrâneos em Portugal é heterogénea e mostra (i) elevada concentração de vértices na área cárstica da bacia Lusitânica; (ii) arestas mais fortes localizadas nesta bacia e (iii) menor número de abrigos a norte, com um a servir como ponte de contacto e um isolado na zona costeira. O cálculo da estrutura de aglomeração otimizada resultou em 5 grupos com forte ligação às áreas geográficas do país e modularidade de 0.54. A comparação da estrutura de rede e ajuste de distribuição evidenciam que a rede MiniS apresenta distribuição normal e métricas semelhantes ao modelo sem escala e “small-world”. A lista de 11 abrigos (HRR) mostra vários abrigos com forte influência em múltiplas métricas e alguns apenas em métricas de conectividade, ou seja, a agir como pontes de ligação entre outros abrigos. A análise de robustez mostra que na simulação aleatória a remoção de 23% dos vértices resulta em 50% de perda de conectividade. No entanto, nas simulações de remoção de nós pela ordem de grau e de “betweenness” e grau é apenas necessário remover 3.48 e 4.4% (4 abrigos) respetivamente, e para as de “hub” e autoridades é apenas necessário remover 11 e 9%, respetivamente, para obter valores de perda semelhantes. As simulações de perda de conectividade associadas a fogos florestais revelaram vulnerabilidade próxima dos valores obtidos com a simulação aleatória para qualquer das distâncias usadas. Apesar disso, a análise dos HRR mostra que ocorrem entre eles fogos simultâneos entre 12.2% (4) a 100% (33) dos anos, dependendo do raio de distância analisado. A análise de uso do solo revelou que apenas a simulação da categoria florestas resulta em perdas de conectividade maiores que a simulação aleatória, onde a remoção de 5% dos vértices (5 abrigos) resulta em perdas de conectividade de 25%. Paralelamente, a análise comparativa mostrou que os HRR têm valores superiores de floresta, e menor percentagem de espaços artificiais. Com recurso a uma base de dados de 33 anos, este trabalho analisa a maior rede espacial de morcegos publicada até o momento. As características da rede MiniS mostram que as propriedades sem escala também estão presentes nas redes de abrigos de morcegos, embora a nossa rede também apresente características “small-world”. Estes resultados aumentam a evidência da presença de redes com propriedades sem escala na natureza, contribuindo para este tópico. Os nós identificados como “hubs” e autoridades presentes na MiniS tomam a forma de abrigos de maternidade ou hibernação provavelmente resultante do modo de recolha de dados e importância destas fases no ciclo de vida da espécie. Por sua vez a modularidade e número de grupos na rede foi inferior ao esperado derivado dos diferentes padrões de migração individuais, maturidade sexual, sucesso reprodutivo e sexo. Apesar destes fatores há uma clara relação geográfica no padrão de aglomeração que poderá estar a evidenciar o equilíbrio de custo-benefício de voos de longa distância. Apesar da vulnerabilidade a ataques direcionados a “hubs”, observou-se que o grau e “betweenness” apresentam maiores e mais rápidas perdas de conectividade da rede, demonstrando que apesar da importância dos “hubs” existem outras métricas que podem indicar maiores perdas de conectividade na rede. A MiniS não apresentou interações significantes entre conectividade e fogos florestais, no entanto e como documentado previamente, a interpretação deste resultado é dependente da espécie, tempo e proximidade ao fogo. A análise dos HRR revelou ainda que estes eventos podem simular um padrão de ataque direcionado. Apesar dos resultados não apontarem perdas de conectividade perante fogos florestais, cenários futuros onde estes eventos sejam mais frequentes e severos podem resultar em impactos na conectividade da rede. Os resultados da análise do uso de solo realçam o papel que as florestas têm na manutenção da conectividade da rede. Esta ameaça é amplificada pela tendência decrescente de florestas em Portugal especialmente na região centro onde se encontram a maioria dos abrigos. Estes fatores podem levar a diminuição da fitness populacional e fragmentação da rede. No entanto, é importante realçar que ambas as análises (fogos florestais e alterações do uso do solo) foram feitas com o objetivo de ilustrar o potencial desta metodologia para avaliar impactos de fatores ambientais na conectividade. Para além disso, e por não haver estudos que quantifiquem o impacto real destes fatores na utilização dos abrigos de morcegos cavernícolas utilizaram-se simulações extremas onde os abrigos afetados deixariam totalmente de ser utilizados. O presente trabalho aplica técnicas de análise de redes para criar a primeira rede abrangente de movimentos de morcegos de Portugal. A rede apresenta características sem escala, presença de “hubs” e permitiu realizar simulações de conectividade e testes de robustez. Estas análises sugerem que a conectividade da rede não é impactada por fogos florestais, mas que podem afetar abrigos importantes simultânea e sistematicamente. Os resultados enfatizam também a importância das florestas para a manutenção da conectividade da MiniS. Esta rede permite também avaliar o impacto de outros fatores ambientais como a remoção de abrigos por abatimento ou perturbação antropogénica direta. A utilização desta rede para suporte à gestão permitirá a avaliação das presentes medidas impostas em áreas Natura 2000, bem como na modelação de comportamento da rede em cenários futuros.Despite the costs involved with long-distance movement, this behaviour is found across multiple vertebrate groups. Therefore, understanding the spatial structure associated with animal movement and how environmental factors might impact their connectivity is critical for conservation management. Since network theory is based on connectivity features, its tools can be useful for analyses of animal movement. Thus, we aimed to create and determine the structure of a bat roost network; and to assess its robustness to environmental factors - wildfires, and land-use change- by simulating node deletion. The large-scale bat roost network, MiniS, was created using a large dataset of Miniopterus schreibersii movements’ (n= 70 090) across southwestern Iberia. Using network metrics, we also compiled a list of the highest-ranking roost (HRR). We then analyzed the network connectivity losses associated with wildfire history or land cover change through node removal simulations. Additionally, we compared the values for these two environmental factors between the HRR and the network average. The MiniS has 99 roosts and presents scale-free and small-world characteristics following a log-normal degree distribution. The connectivity simulations showed that the network is resilient to wildfires, however, the HRR analysis demonstrated that wildfires happened near several vital roosts within the same year, a scenario mimicking a targeted attack. Conversely, land cover simulations showed that the network is vulnerable to the removal of higher forest cover roosts: removing only 5% of nodes causes 25% connectivity loss. However, it is noteworthy that both analyses (forest wildfire history and land use changes) were made to illustrate the potential of the methodology and that the simulations use the extreme situation, in which the affected roosts would be abandoned. This research demonstrates that network theory is an asset in creating model networks, which can be used to simulate impact scenarios and produce conservation guidelines

Forcing contacts between mitochondria and the endoplasmic reticulum extends lifespan in a Drosophila model of Alzheimer’s disease.

cells are complex systems containing internal compartments with specialised functions. Among these compartments, the endoplasmic reticulum (ER) plays a major role in processing proteins for modification and delivery to other organelles, whereas mitochondria generate energy in the form of ATP. Mitochondria and the ER form physical interactions, defined as mitochondria-ER contact sites (MERCS) to exchange metabolites such as calcium ions (Ca2+) and lipids. Sites of contact between mitochondria and the ER can regulate biological processes such as ATP generation and mitochondrial division. The interactions between mitochondria and the ER are dynamic and respond to the metabolic state of cells. Changes in MERCS have been linked to metabolic pathologies such as diabetes, neurodegenerative diseases and sleep disruption. Here we explored the consequences of increasing contacts between mitochondria and the ER in flies using a synthetic linker. We showed that enhancing MERCS increases locomotion and extends lifespan. We also showed that, in a Drosophila model of Alzheimer’s disease linked to toxic amyloid beta (Aβ), linker expression can suppress motor impairment and extend lifespan. We conclude that strategies for increasing contacts between mitochondria and the ER may improve symptoms of diseases associated with mitochondria dysfunction.MRC RG9452

Dietary Composition Modulates Brain Mass and Solubilizable ABeta Levels in a Mouse Model of Aggressive Alzheimer\u27s Amyloid Pathology

Objective: Alzheimer\u27s disease (AD) is a progressive neurodegenerative disease of the central nervous system (CNS). Recently, an increased interest in the role diet plays in the pathology of AD has resulted in a focus on the detrimental effects of diets high in cholesterol and fat and the beneficial effects of caloric restriction. The current study examines how dietary composition modulates cerebral amyloidosis and neuronal integrity in the TgCRND8 mouse model of AD. Methods: From 4 wks until 18 wks of age, male and female TgCRND8 mice were maintained on one of four diets: (1) reference (regular) commercial chow; (2) high fat/low carbohydrate custom chow (60 kcal% fat/30 kcal% protein/10 kcal% carbohydrate); (3) high protein/low carbohydrate custom chow (60 kcal% protein/30 kcal% fat/10 kcal% carbohydrate); or (4) high carbohydrate/low fat custom chow (60 kcal% carbohydrate/30 kcal% protein/10 kcal% fat). At age 18 wks, mice were sacrificed, and brains studied for (a) wet weight; (b) solubilizable Aβ content by ELISA; (c) amyloid plaque burden; (d) stereologic analysis of selected hippocampal subregions. Results: Animals receiving a high fat diet showed increased brain levels of solubilizable Aβ, although we detected no effect on plaque burden. Unexpectedly, brains of mice fed a high protein/low carbohydrate diet were 5% lower in weight than brains from all other mice. In an effort to identify regions that might link loss of brain mass to cognitive function, we studied neuronal density and volume in hippocampal subregions. Neuronal density and volume in the hippocampal CA3 region of TgCRND8 mice tended to be lower in TgCRND8 mice receiving the high protein/low carbohydrate diet than in those receiving the regular chow. Neuronal density and volume were preserved in CA1 and in the dentate gyrus. Interpretation: Dissociation of Aβ changes from brain mass changes raises the possibility that diet plays a role not only in modulating amyloidosis but also in modulating neuronal vulnerability. However, in the absence of a study of the effects of a high protein/low carbohydrate diet on nontransgenic mice, one cannot be certain how much, if any, of the loss of brain mass exhibited by high protein/low carbohydrate diet-fed TgCRND8 mice was due to an interaction between cerebral amyloidosis and diet. Given the recent evidence that certain factors favor the maintenance of cognitive function in the face of substantial structural neuropathology, we propose that there might also exist factors that sensitize brain neurons to some forms of neurotoxicity, including, perhaps, amyloid neurotoxicity. Identification of these factors could help reconcile the poor clinicopathological correlation between cognitive status and structural neuropathology, including amyloid pathology

Patients’ Experiences of a Sarcoma Diagnosis: A Process Mapping Exercise of Diagnostic Pathways

Patients with sarcoma often report prolonged time to diagnosis, which is attributed to the rarity of sarcoma and the low awareness of pre-diagnostic signs and symptoms. Aims: To describe patients’ experiences of pre-diagnostic signs/symptoms and pathways to diagnosis, including where help was sought, and the processes involved. Methods: Mixed methods involving quantitative, qualitative and inductive thematic analyses using novel process mapping of patient journey data, as reported by the patients. We examined the time from symptom onset to first professional presentation (patient interval, PI), first consultation to diagnostic biopsy, first consultation to diagnosis (diagnostic interval) and first presentation to diagnosis (total interval). Results: A total of 87 interviews were conducted over 5 months in 2017. Of these, 78 (40 males/38 females) were included. The sarcoma subtypes were bone (n = 21), soft tissue (n = 41), head and neck (n = 9) and gastro-intestinal (GIST; n = 7). Age at diagnosis was 13–24 (n = 7), 25–39 (n = 23), 40–64 (n = 34) and 65+ (n = 14) years. The median PI was 13 days (1–4971) and similar between sarcoma subtypes, with the exception of GIST (mPI = 2 days, (1–60). The longest mPI (31 days, range 4–762) was for those aged 13–24 years. The median diagnostic interval was 87.5 (range 0–5474 days). A total of 21 patients were misdiagnosed prior to diagnosis and symptoms were commonly attributed to lifestyle factors. Conclusions: Prolonged times to diagnosis were experienced by the majority of patients in our sample. Further research into the evolution of pre-diagnostic sarcoma symptoms is required to inform awareness interventions

Dietary composition modulates brain mass and solubilizable Aβ levels in a mouse model of aggressive Alzheimer's amyloid pathology

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Objective Alzheimer's disease (AD) is a progressive neurodegenerative disease of the central nervous system (CNS). Recently, an increased interest in the role diet plays in the pathology of AD has resulted in a focus on the detrimental effects of diets high in cholesterol and fat and the beneficial effects of caloric restriction. The current study examines how dietary composition modulates cerebral amyloidosis and neuronal integrity in the TgCRND8 mouse model of AD. Methods From 4 wks until 18 wks of age, male and female TgCRND8 mice were maintained on one of four diets: (1) reference (regular) commercial chow; (2) high fat/low carbohydrate custom chow (60 kcal% fat/30 kcal% protein/10 kcal% carbohydrate); (3) high protein/low carbohydrate custom chow (60 kcal% protein/30 kcal% fat/10 kcal% carbohydrate); or (4) high carbohydrate/low fat custom chow (60 kcal% carbohydrate/30 kcal% protein/10 kcal% fat). At age 18 wks, mice were sacrificed, and brains studied for (a) wet weight; (b) solubilizable Aβ content by ELISA; (c) amyloid plaque burden; (d) stereologic analysis of selected hippocampal subregions. Results Animals receiving a high fat diet showed increased brain levels of solubilizable Aβ, although we detected no effect on plaque burden. Unexpectedly, brains of mice fed a high protein/low carbohydrate diet were 5% lower in weight than brains from all other mice. In an effort to identify regions that might link loss of brain mass to cognitive function, we studied neuronal density and volume in hippocampal subregions. Neuronal density and volume in the hippocampal CA3 region of TgCRND8 mice tended to be lower in TgCRND8 mice receiving the high protein/low carbohydrate diet than in those receiving the regular chow. Neuronal density and volume were preserved in CA1 and in the dentate gyrus. Interpretation Dissociation of Aβ changes from brain mass changes raises the possibility that diet plays a role not only in modulating amyloidosis but also in modulating neuronal vulnerability. However, in the absence of a study of the effects of a high protein/low carbohydrate diet on nontransgenic mice, one cannot be certain how much, if any, of the loss of brain mass exhibited by high protein/low carbohydrate diet-fed TgCRND8 mice was due to an interaction between cerebral amyloidosis and diet. Given the recent evidence that certain factors favor the maintenance of cognitive function in the face of substantial structural neuropathology, we propose that there might also exist factors that sensitize brain neurons to some forms of neurotoxicity, including, perhaps, amyloid neurotoxicity. Identification of these factors could help reconcile the poor clinicopathological correlation between cognitive status and structural neuropathology, including amyloid pathology.Published versio

Remapeamento sensorial: uma possível opção de terapia

Os receptores sensoriais humanos são morfologicamente especializados para realizar a transdução de estímulos específicos para o encéfalo. Entretanto, quando ocorre uma lesão, principalmente, na medula espinal, que pode ser de origem traumática e não traumática, provocam diversos graus de déficits sensoriais, disfunção autônoma, motora e esfincteriana, abaixo do nível da lesão. Com base nisso, uma nova modalidade terapêutica está sendo proposto pelo neurocientista Miguel Nicolelis, que tem como base a interface cérebro máquina, isto é, utilizar-se de outras vias para que as informações possam chegar no córtex cerebral e assim serem processadas conscientemente. conscientementeThe human sensory receptors are morphologically specialized to transduce specific stimuli into the brain. However, when an injury occurs, mainly in the spinal cord, which can be of traumatic or non-traumatic origin, it provokes various degrees of sensory deficits, autonomic, motor and sphincter dysfunction below the level of the injury. Based on this, a new therapeutic modality is being proposed by neuroscientist Miguel Nicolelis, which is based on the brain-machine interface, that is, using other pathways so that the information can reach the cerebral cortex and thus be consciously processed

Effectiveness of pedometer-based walking programmes in improving some modifiable risk factors of stroke among community-dwelling older adults : a systematic review, theoretical synthesis and meta-analysis

DATA AVAILABILITY STATEMENT: The datasets supporting the conclusions of this article are available in the institutional University of Nigeria repository and will be made easily available on request when required. All requests for the study data should be addressed to the corresponding author via email: [email protected]: Pedometer-based walking programs hold promise as a health promotion strategy for stroke prevention in community-dwelling older adults, particularly when targeted at physical activity-related modifiable risk factors. The question arises: What is the effectiveness of pedometer-based walking program interventions in improving modifiable stroke risk factors among community-dwelling older adults? METHOD: Eight databases were searched up to December 2nd, 2023, following the Preferred Reporting Items for Systematic Review and Meta-Analysis protocol. Inclusion criteria focused on randomized controlled trials (RCTS) involving community-dwelling older adults and reported in English. Two independent reviewers utilized Physiotherapy Evidence Database (PEDro) tool to extract data, assess eligibility, evaluate study quality, and identify potential bias. Standardized mean difference (SMD) was employed as summary statistics for primary —physical activity level —and secondary outcomes related to cardiovascular function (blood pressure) and metabolic syndrome, including obesity (measured by body mass index and waist circumference), fasting blood sugar, glycated hemoglobin, high-density lipoprotein cholesterol (HDL-C), and triglycerides. A random-effects model was used to generate summary estimates of effects. RESULTS: The review analyzed eight studies involving 1546 participants aged 60-85 years, with 1348 successfully completing the studies. Across these studies, pedometer-based walking programs were implemented 2-3 times per week, with sessions lasting 40-60 minutes, over a duration of 4-26 weeks. The risk of bias varied from high to moderate. Our narrative synthesis revealed positive trends in HDL-C levels, fasting blood sugar, and glycated hemoglobin, suggesting improved glycemic control and long-term blood sugar management. However, the impact on triglycerides was only marginal. Primary meta-analysis demonstrated significantly improved physical activity behavior (SMD=0.44,95%CI:0.26, 0.61,p=<0.00001;I2=0%;4 studies; 532 participants) and systolic blood pressure (SMD=-0.34,95%CI:-0.59,-0.09;p=<0.008;I2=65%,2 studies;249 participants), unlike diastolic blood pressure (SMD=0.13,95%CI:-0.13,-0.38,p=0.33; I2=91%; 2 studies; 237 participants). Interventions based on social cognitive, self-efficacy, and self-efficiency theory(ies), and social cognitive theory applied in an ecological framework, were linked to successful physical activity behavior outcomes. CONCLUSION: Pedometer-based walking programs, utilizing interpersonal health behavior theory/ecological framework, enhance physical activity behavior and have antihypertensive effects in community-dwelling older adults. While they do not significantly affect diastolic blood pressure, these programs potentially serve as a primary stroke prevention strategy aligning with global health goals.https://bmcgeriatr.biomedcentral.com/PhysiotherapySDG-03:Good heatlh and well-bein

Plasma high-density lipoprotein cargo is altered in Alzheimer\u27s disease and is associated with regional brain volume

Cholesterol levels have been repeatedly linked to Alzheimer\u27s Disease (AD), suggesting that high levels could be detrimental, but this effect is likely attributed to Low-Density Lipoprotein (LDL) cholesterol. On the other hand, High-Density Lipoproteins (HDL) cholesterol levels have been associated with reduced brain amyloidosis and improved cognitive function. However, recent findings have suggested that HDL-functionality, which depends upon the HDL-cargo proteins associated with HDL, rather than HDL levels, appears to be the key factor, suggesting a quality over quantity status. In this report, we have assessed the HDL-cargo (Cholesterol, ApoA-I, ApoA-II, ApoC-I, ApoC-III, ApoD, ApoE, ApoH, ApoJ, CRP, and SAA) in stable healthy control (HC), healthy controls who will convert to MCI/AD (HC-Conv) and AD patients (AD). Compared to HC we observed an increased cholesterol/ApoA-I ratio in AD and HC-Conv, as well as an increased ApoD/ApoA-I ratio and a decreased ApoA-II/ApoA-I ratio in AD. Higher cholesterol/ApoA-I ratio was also associated with lower cortical grey matter volume and higher ventricular volume, while higher ApoA-II/ApoA-I and ApoJ/ApoA-I ratios were associated with greater cortical grey matter volume (and for ApoA-II also with greater hippocampal volume) and smaller ventricular volume. Additionally, in a clinical status-independent manner, the ApoE/ApoA-I ratio was significantly lower in APOE ε4 carriers and lowest in APOE ε4 homozygous. Together, these data indicate that in AD patients the composition of HDL is altered, which may affect HDL functionality, and such changes are associated with altered regional brain volumetric data

Decrease in p3-Alcb37 and p3-Alcb40, products of Alcadein b generated by g-secretase cleavages, in aged monkeys and patients with Alzheimer’s disease

Introduction Neuronal p3-Alcβ peptides are generated from the precursor protein Alcadein β (Alcβ) through cleavage by α- and γ-secretases of the amyloid β (Aβ) protein precursor (APP). To reveal whether p3-Alcβ is involved in Alzheimer\u27s disease (AD) contributes for the development of novel therapy and/or drug targets. Methods We developed new sandwich enzyme-linked immunosorbent assay (sELISA) systems to quantitate levels of p3-Alcβ in the cerebrospinal fluid (CSF). Results In monkeys, CSF p3-Alcβ decreases with age, and the aging is also accompanied by decreased brain expression of Alcβ. In humans, CSF p3-Alcβ levels decrease to a greater extent in those with AD than in age-matched controls. Subjects carrying presenilin gene mutations show a significantly lower CSF p3-Alcβ level. A cell study with an inverse modulator of γ-secretase remarkably reduces the generation of p3-Alcβ37 while increasing the production of Aβ42. Discussion Aging decreases the generation of p3-Alcβ, and further significant decrease of p3-Alcβ caused by aberrant γ-secretase activity may accelerate pathogenesis in AD

Decrease in p3-Alcb37 and p3-Alcb40, products of Alcadein b generated by g-secretase cleavages, in aged monkeys and patients with Alzheimer’s disease

Introduction Neuronal p3-Alcβ peptides are generated from the precursor protein Alcadein β (Alcβ) through cleavage by α- and γ-secretases of the amyloid β (Aβ) protein precursor (APP). To reveal whether p3-Alcβ is involved in Alzheimer\u27s disease (AD) contributes for the development of novel therapy and/or drug targets. Methods We developed new sandwich enzyme-linked immunosorbent assay (sELISA) systems to quantitate levels of p3-Alcβ in the cerebrospinal fluid (CSF). Results In monkeys, CSF p3-Alcβ decreases with age, and the aging is also accompanied by decreased brain expression of Alcβ. In humans, CSF p3-Alcβ levels decrease to a greater extent in those with AD than in age-matched controls. Subjects carrying presenilin gene mutations show a significantly lower CSF p3-Alcβ level. A cell study with an inverse modulator of γ-secretase remarkably reduces the generation of p3-Alcβ37 while increasing the production of Aβ42. Discussion Aging decreases the generation of p3-Alcβ, and further significant decrease of p3-Alcβ caused by aberrant γ-secretase activity may accelerate pathogenesis in AD