Perineuronale Netze (PN) sind eine spezialisierte Form der neuronalen extrazellulären Matrix. Es wird vermutet, dass sie neuroprotektive Eigenschaften besitzen und die von ihnen umschlossenen Neurone gegenüber Degeneration schützen. Mehrere Studien untersuchten bereits die PN in Zusammenhang mit der Pathologie der Alzheimer-Erkrankung. Für die Frontotemporalen Demenzen, die nach der Alzheimer-Erkrankung und der vaskulären Demenz zu den häufigsten dementiellen Erkrankungen gehören, ist die Beziehung von PN und Tau-Protein (TP)-Pathologie noch nicht untersucht worden. Die Dissertation beschäftigt sich mit der Korrelation von netztragenden Neuronen mit TP-Pathologie in einem Mausmodel der Frontotemporalen Demenz mit Parkinsonismus des Chromosoms 17 (FTDP-17). Sie geht der Frage nach, ob netztragende Neuronen vor Degeneration und intrazellulären Ablagerungen von verändertem TP, in Form von Hyperphosphorylierungen (HP) und Neurofibrillären Tangles (NFT), geschützt sind. Mit Hilfe immunhistochemischer Fluoreszenzmarkierung und Western Blot wurden die Gehirne transgener Mäuse mit der P301L-Mutation des TP im Alter von drei und achteinhalb Monaten untersucht. Dabei wurden sechs Hirnregionen ausgewählt: Primärer Somatosensorischer Kortex (PSC), Entorhinaler Kortex (EC), Hippokampus (Hipp), Pars magnocellularis des Nucleus ruber (NR-m), Pars reticulata der Substantia nigra (SN-r) und Motorischer Trigeminuskern (Mo5). Die Untersuchungen zeigen, dass die PN bei der FTDP-17 die Neurone nicht explizit vor TP-Pathologie schützen. Jedoch kommt es zu keiner signifikanten Reduktion der netztragenden Zellen im Altersgang, sodass eine neuroprotektive Funktion der PN weiterhin vermutet werden kann.

O presente estudo comparou o efeito do tratamento crônico com lítio em doses subterapêuticas (0,02mM e 0,2mM) e dose terapêutica (2mM) em cultura primária de neurônios corticais e hipocampais. As amostras foram analisadas e comparadas com o grupo controle (sem tratamento) tanto para os neurônios corticais, como para os neurônios hipocampais. O objetivo do estudo foi: 1) avaliar, nessas culturas celulares, a atividade de diferentes quinases (PKA, CaMKII, AKT e GSK3beta), diferentes sítio de fosforilação da Tau (Ser, 199, 205, 214, 396, C-terminal e seis isoformas), a partir da inibição da PLA2 pelo lítio; 2) Investigar as vias de sinalização envolvidas na modulação do estado de fosforilação da proteína tau a partir da inibição da PLA2 em culturas primárias de neurônios; 3) avaliar, simultaneamente, a expressão de fatores neurotróficos (BDNF) e citocinas (GM-CSF, IL-1b, IL-2, IL-4, IL-5, IL6, IL-10, IL-12, IFN-y e TNF-alfa) mediante o tratamento de neurônios primários com lítio e 4) avaliar expressão gênica por microarray das culturas tratadas com diferentes doses, subterapêuticas e terapêutica, de cloreto de lítio. Nossos resultados sugerem uma dissociação de efeitos em neurônios corticais dos observados em neurônios hipocampais. O lítio aumentou a atividade enzimática da iPLA2 e da cPLA2, tanto em neurônios corticais como em neurônios hipocampais. A atividade da GSK3beta foi inibida pelo tratamento crônico com lítio em neurônios hipocampais e apresentou efeito contrário em neurônios corticais. Observamos comportamentos diferentes das diferentes proteínas analisadas em culturas de neurônios corticais e hipocampais, e não tivemos significância estatística para as alterações na proteína tau. O tratamento nas doses subterapêuticas aumentou a secreção de citocinas pró-inflamatórias tanto em neurônios corticais quanto em neurônios hipocampais / The present study compared the effect of lithium chronic treatment with subtherapeutic doses (0.02mM and 0.2mM) and therapeutic dose (2mM) in primary cortical and hippocampal neurons cell culture. This samples were analyzed and compared with the control group (no treatment). The study\'s goal was: 1) to evaluate in these Cell Culture a different activity kinases (PKA, CaMKII, AKT and GSK3beta), different phosphorylation site of the Tau (199, 205, 214, 396, C-terminal and Six isoforms) and PLA2 inhibition; 2) To investigate how signaling pathways involved in modulation of tau phosphorylation from the inhibition of PLA2 in primary cultures of neurons; 3) analyze an expression of neurotrophic factors (BDNF) and cytokines (GM-CSF, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IFNy TNFalfa 4) to evaluate gene expression via microarray with different doses of lithium treatment. Our results suggest a dissociation effects on cortical and hippocampal neurons cell culture. Lithium increased the enzyme activity of iPLA2 and cPLA2, in both cortical and hippocampal neurons. The GSK3beta the activity was inhibited by chronic treatment with lithium in hippocampal neurons and presented contrary effect on cortical neurons. We observe not statistics significance on tau protein. The treatment at subtherapeutic and therapeutic doses increased the secretion of pro and anti-inflammatory cytokines both in cortical and hippocampal neurons

No description available.

M. Niemann-Pick Typ C (NPC) ist eine juvenile Demenz mit intrazellulärer Anreicherung von freiem Cholesterin, M. Alzheimer (AD) eine senile Demenz, die mit einem Polymorphismus im Gen des Cholesterintransportproteins Apolipoprotein E (ApoE) assoziiert ist. Bei beiden Erkrankungen treten im Gehirn zahlreiche neurofibrilläre Tangles (NFT), bestehend aus Protein Tau, auf. Es sollte mit einer für freies Cholesterin spezifischen Filipin-Färbung herausgefunden werden, ob sich bei beiden Erkrankungen der Cholesteringehalt Tangle-tragender Neurone von dem Tangle-freier unterscheidet. Zur Verfügung standen diverse Teile aus dem Zentralen Nervensystem von 5 NPC- und Gyri temporales superficiales von 9 AD-Fällen. In Material von 3 NPC-Fällen und 1 AD-Fall fanden sich intraneuronale, mit Tangles assoziierte Cholesterinakkumulationen. In 3 AD-Fällen fanden sich außerdem Cholesterinakkumulationen in Assoziation mit Senilen Plaques. Der Cholesteringehalt Tangle-tragender Neurone war in 6 Regionen der NPC-Fälle und in 3 AD-Fällen erhöht. Für alle Neuronenpaare der AD-Fälle insgesamt ergab sich ein erhöhter Cholesteringehalt des Tangle-tragenden Neurons. Cholesterinspeicherung im NPC-Hirn könnte über oxidativen Stress oder eine Veränderung der cholesterinabhängigen Signaltransduktion zur Tangle-Bildung führen. Argumente für die Unterstützung der Tangle-Bildung durch Cholesterin über oxidativen Stress und veränderte Signaltransduktion in AD werden angeführt. Diese Untersuchung erlaubt, neue Hypothesen zu gemeinsamen Mechanismen der Tangle-Entstehung in AD und NPC zu formulieren. / Niemann-Pick type C disease (NPC) is a juvenile dementia with intracellular accumulation of free cholesterol, whereas Alzheimer s disease (AD) is a senile dementia associated with a gene polymorphism of a cholesterol transport protein, apolipoprotein E (apoE). In both conditions, there are abundant neurofibrillary tangles (NFT) in brain, consisting of protein tau. This study addresses the issue whether cholesterol content of tangle-bearing neurons is the same compared to tangle-free neurons, in both diseases. For this purpose, staining with the free cholesterol-specific fluorochrome filipin was used. Several CNS tissue specimen of 5 NPC cases and superior temporal gyri of 9 AD cases were available. In 3 NPC cases and 1 AD case, intraneuronal cholesterol accumulation were found associated with neurofibrillary tangles. Furthermore, cholesterol accumulations were found associated with senile plaques in 3 AD cases. Cholesterol content of tangle-bearing neurons was increased in 6 regions of the NPC cases and in 3 AD cases. For all neurons analysed in AD, the tangle-bearing neuron showed more cholesterol than the adjacent tangle-free neuron. Cholesterol storage in NPC brain could lead to neurofibrillary degeneration by enhancing oxidative stress or by alterating cholesterol-dependent signal transduction. Cholesterol accumulation in AD neurons could lead to neurofibrillary degeneration by the same mechanisms. This study allows the creation of new hypotheses concerning common mechanisms of neurofibrillary degeneration in both Niemann-Pick type C and Alzheimer s diseases.

La maladie d'Alzheimer (MA) est une pathologie neurodégénérative s'exprimant par des troubles de la mémoire et un déclin cognitif évoluant progressivement vers un stade de démence incurable. Elle représente la cause principale de syndrome démentiel puisque l'on estime qu'elle est à l'origine de plus de 70% des cas de démences. Du fait de sa prévalence élevée après 60 ans, la MA représente un problème majeur de santé publique. La MA se caractérise par la présence de deux types de lésions cérébrales : les dégénérescences neurofibrillaires (DNF) et les plaques amyloïdes. Cependant, aucun consensus clair ne se dégage concernant les relations qui lient les deux types de lésions. Leur présence ne peut être mise en évidence que par un examen post-mortem. La MA est par définition une pathologie évolutive, cet examen ne permet donc pas de caractériser de manière adéquate les processus dynamiques qui sous-tendent cette pathologie. La mise au point de techniques d'imagerie non invasives permettant de réaliser un suivi longitudinal in vivo de ces lésions s'avère déterminante dans la compréhension de la physiopathologie de la MA. Les travaux effectués au cours de cette thèse ont pour objectif la mise au point de nouveaux radiotraceurs des lésions amyloïdes et neurofibrillaires pour l'imagerie nucléaire. Cette approche se distingue en trois parties. Dans un premier temps, nous avons validé un modèle animal de la MA: les souris transgéniques 3xTgAD. Dans un second temps, nous avons réalisé l'évaluation biologique de différents radiotraceurs connus sur ce modèle animal : le 99mTc-HMPAO, le 18F-FDG et le 125I-IMPY. Enfin, nous avons initié le développement de plusieurs nouveaux traceurs pour permettre le suivi de la MA in vivo : les para-sulfonato-calixarènes qui présentent une affinité intéressante pour les plaques amyloïdes, les composés COB qui inhibent la formation des agrégats de peptides amyloïdes in vitro ainsi qu'un peptide, A93, associé à un vecteur qui pourrait interagir avec les dégénérescences neurofibrillaires. / Alzheimer's disease (AD) is a neurodegenerative pathology showing cognitive and memory disorders which progress toward an incurable demential state. AD represents the principle cause of the dementia syndrome and it is estimated that AD is involved in 70% of dementia cases. AD prevalence is high in the over 60 years old population. This elevated prevalence is associated with an increasing number of elderly people. AD is therefore a major public health concern. AD is characterized by two types of specific cerebral lesions: neurofibrillary tangles (NFT) and amyloid plaques. However, there is no consensus on the links between these two types of lesions. To date, their presence can only be evaluated by a post-mortem examination. AD being a progressive pathology, this examination cannot be used to fully characterize the dynamic processes involved in AD. In this context, the development of non invasive imaging techniques to monitor the lesions progression in vivo could be determinant in AD pathophysiology understanding. Our objective is to develop new tracers of amyloid and neurofibrillary lesions for nuclear imaging. The first part of this study was dedicated to the validatation of an AD animal model: Transgenic 3xTgAD mice. The second part of this thesis focuses on the appreciatiation of the biological comportement of several known radiotracers of AD on this animal model. In the third part of this work, we initiate the development of several new tracers of AD-specific lesions. The para-sulfonato- calixarenes and the COB compounds for amyloid plaques detection and a peptide named A93, associated to a vector for the study of neurofibrillary tangles.

Perineuronale Netze (PN) sind eine spezialisierte Form der neuronalen extrazellulären Matrix. Es wird vermutet, dass sie neuroprotektive Eigenschaften besitzen und die von ihnen umschlossenen Neurone gegenüber Degeneration schützen. Mehrere Studien untersuchten bereits die PN in Zusammenhang mit der Pathologie der Alzheimer-Erkrankung. Für die Frontotemporalen Demenzen, die nach der Alzheimer-Erkrankung und der vaskulären Demenz zu den häufigsten dementiellen Erkrankungen gehören, ist die Beziehung von PN und Tau-Protein (TP)-Pathologie noch nicht untersucht worden. Die Dissertation beschäftigt sich mit der Korrelation von netztragenden Neuronen mit TP-Pathologie in einem Mausmodel der Frontotemporalen Demenz mit Parkinsonismus des Chromosoms 17 (FTDP-17). Sie geht der Frage nach, ob netztragende Neuronen vor Degeneration und intrazellulären Ablagerungen von verändertem TP, in Form von Hyperphosphorylierungen (HP) und Neurofibrillären Tangles (NFT), geschützt sind. Mit Hilfe immunhistochemischer Fluoreszenzmarkierung und Western Blot wurden die Gehirne transgener Mäuse mit der P301L-Mutation des TP im Alter von drei und achteinhalb Monaten untersucht. Dabei wurden sechs Hirnregionen ausgewählt: Primärer Somatosensorischer Kortex (PSC), Entorhinaler Kortex (EC), Hippokampus (Hipp), Pars magnocellularis des Nucleus ruber (NR-m), Pars reticulata der Substantia nigra (SN-r) und Motorischer Trigeminuskern (Mo5). Die Untersuchungen zeigen, dass die PN bei der FTDP-17 die Neurone nicht explizit vor TP-Pathologie schützen. Jedoch kommt es zu keiner signifikanten Reduktion der netztragenden Zellen im Altersgang, sodass eine neuroprotektive Funktion der PN weiterhin vermutet werden kann.

As septinas fazem parte de uma família de proteínas de ligação ao nucleotídeo guanina. As septinas têm mostrado ter um papel importante na citocinese e outros processos celulares, incluindo a determinação da polaridade celular e reorganização do citoesqueleto. Todos os membros da família de septinas são compostos por três domínios: um N-terminal variável, um domínio central GTPase e uma região C-terminal que inclui sequências de coiled-coil. Septinas possuem uma característica de polimerizarem para formar complexos hetero-oligoméricos altamente organizados, in vivo e in vitro. Estruturas homo-oligoméricas também foram observadas, embora sua função ainda não esteja bem estabelecida. A Septina 2 humana (SEPT2) se acumula no sulco de clivagem de células em divisão, desde a anáfase até a telófase, além de interagir com a actina, e também está envolvida em doenças neurodegenerativas, como mal de Azheimer. Nesse estudo, a ORF que codifica SEPT2, bem como os fragmentos que codificam seus domínios, foram clonados, expressos em E.coli e purificados por cromatografia de afinidade e cromatografia de exclusão molecular. Os produtos foram analisados por espectroscopia de dicroísmo circular, espalhamento de luz a ângulo fixo e espectroscopia de fluorescência extrínseca, usando Tioflavina-T, que é um marcador clássico para fibras amilóides. Em todos os casos, os produtos formaram homodímeros in vitro, e também agregaram em temperaturas fisiológicas. O desenovelamento térmico das proteínas recombinantes revelou a presença de uma população intermediária de desenovelamento, rica em folhas-β, e que ligam Tioflavina-T, sugerindo uma estrutura amiloidogênica para essa proteína, confirmada pelos programas de predição TANGO e WALTZ. Imagens dessas fibras foram obtidas usando Microscopia eletrônica de Transmissão, evidenciando uma agregação organizada das proteínas. Além disso, usando monocamadas de Langmuir, foi possível confirmar a ligação específica de SEPT2 ao fosfolipídeo fosfatidilinositol 4,5-bifosfato (PtdIns(4,5)P2). Essa ligação específica mantém a estrutura secundária de SEPT2, observada pela técnica PM-IRRAS, algo que não ocorre caso o lipídio seja inespecífico, sugerindo uma associação de SEPT2 com a membrana plasmática e podendo ter um papel na regulação das septinas. Por meio da técnica de duplo híbrido em levedura, identificamos proteínas que interagem com a SEPT2, como a MPBI e a DCTN2, auxiliando na elucidação de processos em que a SEPT2 possa participar. O conjunto dos resultados sobre a estabilidade, os processos de agregação de SEPT2 e a identificação de novos parceiros protéicos de interação, obtidos nesse trabalho, contribuíram para o melhor entendimento da função da SEPT2 e de seu envolvimento em desordens neurodegerenativas. / Septins are members of a conserved group of GTP-binding and filament-forming proteins. They are involved in a variety of cellular processes, such as microtubule regulation, vesicle trafficking, the formation of scaffolding platforms and actin dynamics. Human Septin 2 (SEPT2) has an N-terminal polybasic region responsible for lipid binding, a GTPase domain, and a C-terminal domain. SEPT2 is essential for cytokinesis and it is found in many tissues, mainly in the brain. Together with SEPT1 and SEPT4, it is accumulated in deposits known as neurofibrillary tangles in Alzheimers disease, which is evidence that SEPT2 may be involved in this process. In this study, the human SEPT2, and its domains, were cloned, expressed in E.coli and purified by affinity and size-exclusion chromatographies. The proteins form homodimers in vitro, suggesting that the GTPase domain is enough to promote the oligomerization. Thermal unfolding revealed the formation of aggregates under physiological conditions, which have the ability to bind a specific amyloid dye, Thioflavin-T, suggesting them to be an amyloidal fiber. Besides, in silico prediction programs, TANGO and WALTZ, corroborate that SEPT2 contain regions with high probability of aggregation and amyloidogenic formation, respectively. Moreover, we observed 20-50 nm thick filamentous structures by electron microscopy of negatively stained. Using Langmuir monolayers at the cell membrane lipid packing, SEPT2 and SEPT2NG bound to the phospholipid phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Results from in situ PM-IRRAS experiments indicated that the secondary structure of SEPT2 is preserved upon interacting with PtdIns(4,5)P2, but not when interacting with DPPC - which is not specific for SEPT2 - at the air/water interface suggesting an association with the plasma membrane and a role in septin regulation. Furthermore, we also identified protein partners of SEPT2, from both human leukocyte and brain fetal cDNA libraries, using the yeast two-hybrid system. SEPT2 was shown to interact with: septins 6 and 4; a serine-protease and a MAP inhibitory protein; an ubiquitin-conjugating enzyme; and proteins related to cellular division. Thus, taken together this study contributed for the knowledgment of the stability and the aggregation kinetic of the SEPT2, leading to a better understanding of this protein and their role in neurodegenerative disorders.

As septinas fazem parte de uma família de proteínas de ligação ao nucleotídeo guanina. As septinas têm mostrado ter um papel importante na citocinese e outros processos celulares, incluindo a determinação da polaridade celular e reorganização do citoesqueleto. Todos os membros da família de septinas são compostos por três domínios: um N-terminal variável, um domínio central GTPase e uma região C-terminal que inclui sequências de coiled-coil. Septinas possuem uma característica de polimerizarem para formar complexos hetero-oligoméricos altamente organizados, in vivo e in vitro. Estruturas homo-oligoméricas também foram observadas, embora sua função ainda não esteja bem estabelecida. A Septina 2 humana (SEPT2) se acumula no sulco de clivagem de células em divisão, desde a anáfase até a telófase, além de interagir com a actina, e também está envolvida em doenças neurodegenerativas, como mal de Azheimer. Nesse estudo, a ORF que codifica SEPT2, bem como os fragmentos que codificam seus domínios, foram clonados, expressos em E.coli e purificados por cromatografia de afinidade e cromatografia de exclusão molecular. Os produtos foram analisados por espectroscopia de dicroísmo circular, espalhamento de luz a ângulo fixo e espectroscopia de fluorescência extrínseca, usando Tioflavina-T, que é um marcador clássico para fibras amilóides. Em todos os casos, os produtos formaram homodímeros in vitro, e também agregaram em temperaturas fisiológicas. O desenovelamento térmico das proteínas recombinantes revelou a presença de uma população intermediária de desenovelamento, rica em folhas-β, e que ligam Tioflavina-T, sugerindo uma estrutura amiloidogênica para essa proteína, confirmada pelos programas de predição TANGO e WALTZ. Imagens dessas fibras foram obtidas usando Microscopia eletrônica de Transmissão, evidenciando uma agregação organizada das proteínas. Além disso, usando monocamadas de Langmuir, foi possível confirmar a ligação específica de SEPT2 ao fosfolipídeo fosfatidilinositol 4,5-bifosfato (PtdIns(4,5)P2). Essa ligação específica mantém a estrutura secundária de SEPT2, observada pela técnica PM-IRRAS, algo que não ocorre caso o lipídio seja inespecífico, sugerindo uma associação de SEPT2 com a membrana plasmática e podendo ter um papel na regulação das septinas. Por meio da técnica de duplo híbrido em levedura, identificamos proteínas que interagem com a SEPT2, como a MPBI e a DCTN2, auxiliando na elucidação de processos em que a SEPT2 possa participar. O conjunto dos resultados sobre a estabilidade, os processos de agregação de SEPT2 e a identificação de novos parceiros protéicos de interação, obtidos nesse trabalho, contribuíram para o melhor entendimento da função da SEPT2 e de seu envolvimento em desordens neurodegerenativas. / Septins are members of a conserved group of GTP-binding and filament-forming proteins. They are involved in a variety of cellular processes, such as microtubule regulation, vesicle trafficking, the formation of scaffolding platforms and actin dynamics. Human Septin 2 (SEPT2) has an N-terminal polybasic region responsible for lipid binding, a GTPase domain, and a C-terminal domain. SEPT2 is essential for cytokinesis and it is found in many tissues, mainly in the brain. Together with SEPT1 and SEPT4, it is accumulated in deposits known as neurofibrillary tangles in Alzheimers disease, which is evidence that SEPT2 may be involved in this process. In this study, the human SEPT2, and its domains, were cloned, expressed in E.coli and purified by affinity and size-exclusion chromatographies. The proteins form homodimers in vitro, suggesting that the GTPase domain is enough to promote the oligomerization. Thermal unfolding revealed the formation of aggregates under physiological conditions, which have the ability to bind a specific amyloid dye, Thioflavin-T, suggesting them to be an amyloidal fiber. Besides, in silico prediction programs, TANGO and WALTZ, corroborate that SEPT2 contain regions with high probability of aggregation and amyloidogenic formation, respectively. Moreover, we observed 20-50 nm thick filamentous structures by electron microscopy of negatively stained. Using Langmuir monolayers at the cell membrane lipid packing, SEPT2 and SEPT2NG bound to the phospholipid phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Results from in situ PM-IRRAS experiments indicated that the secondary structure of SEPT2 is preserved upon interacting with PtdIns(4,5)P2, but not when interacting with DPPC - which is not specific for SEPT2 - at the air/water interface suggesting an association with the plasma membrane and a role in septin regulation. Furthermore, we also identified protein partners of SEPT2, from both human leukocyte and brain fetal cDNA libraries, using the yeast two-hybrid system. SEPT2 was shown to interact with: septins 6 and 4; a serine-protease and a MAP inhibitory protein; an ubiquitin-conjugating enzyme; and proteins related to cellular division. Thus, taken together this study contributed for the knowledgment of the stability and the aggregation kinetic of the SEPT2, leading to a better understanding of this protein and their role in neurodegenerative disorders.

No description available.

Alzheimers sjukdom är en smygande neurodegenerativ demenssjukdom som främst drabbar äldre och som karakteriseras av uppkomsten av amyloidplack och neurofibriller i hjärnan. De vanligaste symptomen är demens, kognitiva problem, inbillningar och aggressivitet. Alzheimer förekommer i två olika former, presenil och senil alzheimer. Den fullständiga mekanismen bakom alzheimer är ännu okänd men två proteiner, beta-amyloid och tau, anses ligga bakom orsaken till alzheimer. Ett tredje inblandat protein som man funnit via genetisk analys är apolipoprotein E. Idag är alzheimer ett växande problem, detta i takt med att världens befolkning blir allt äldre. En problematik finns idag då den symptomatiska behandling som finns mot alzheimer anses vara otillräcklig, ett botemedel eftersträvas därför. Immunterapi är ett botemedel som man i framtiden hoppas kunna erbjuda, detta i form av ett aktivt eller passivt vaccin verksamt mot beta-amyloid. Forskning för att finna ett sådant pågår därför just nu. AN-1792 (aktivt vaccin), CAD106 (aktivt vaccin), Bapineuzumab (passivt vaccin) och Solanezumab (passivt vaccin) är fyra vaccin som har tagits fram och testats på människor. I de vaccinstudier som gjorts har motgångar stötts på men även framgångar gjorts. AN-1792 är det vaccin som visat sig vara effektivast men med svåra biverkningar medan CAD106 är det vaccin som visat sig vara mindre effektivt men säkrast. Bapineuzumab och Solanezumab visade sig däremot båda två vara overksamma. Då flera av de vaccin som framställts har varit verksamma mot amyloidplack anser forskare att ett framtida vaccin mot alzheimer är möjligt att framställa. / Alzheimer’s disease is an insidious neurodegenerative dementia disease that primarily affects elderly and is characterized by the formation of amyloid plaques and neurofibrillary tangles in the brain. The most common symptoms are dementia, cognitive problems, delusions, and aggressiveness. Alzheimer’s occurs in two forms, presenile and senile Alzheimer’s disease. The complete mechanism behind Alzheimer’s is still unknown but two proteins, beta-amyloid and tau, are considered to be behind the cause of Alzheimer’s. A third protein involved that was found through genetic analysis is apolipoprotein E. Today, Alzheimer’s is a growing problem as the world’s population is getting older. A complex of problems exists as the symptomatic treatment available against Alzheimer’s is considered to be insufficient; a cure is therefore aimed at. Immunotherapy is a cure that hopes can be offered, this in the form of an active or a passive vaccine effective against beta-amyloid. Research to find such a vaccine is therefore under progress right now. AN-1792 (active vaccine), CAD106 (active vaccine), Bapineuzumab (passive vaccine), and Solanezumab (passive vaccine) are four vaccines that have been developed and tested on humans. In the vaccine studies that have been done setbacks have been encountered but also successes have been made. AN-1792 is the vaccine proved to be effective but with severe side effects while CAD106 is the vaccine proved to be less effective but safer. Both Bapineuzumab and Solanezumab showed to be ineffective. Since several of the produced vaccines have been active against amyloid plaques scientists believes that a future vaccine against Alzheimer’s disease is possible to make.