Treatment Of Abstract Alzheimer’s Disease Research Articles

Nanoparticles for the potential treatment of Alzheimer’s disease: A physiopathological approach

Abstract Alzheimer’s disease (AD) is a multifactorial neurodegenerative central system disease with a high prevalence among the elderly and is the most common form of dementia. Oxidative stress is crucial on AD pathogenesis and leads to deposition of neurofibrillary tangles and Aβ plaques; therefore, the use of natural antioxidants or ROS scavengers could help avoid the formation of these aggregates. Similarly, Aβ-degrading/anti-aggregating molecules could help arrest AD progression. Otherwise, traditional anti-Alzheimer drugs such as acetylcholinesterase inhibitors help improve memory and attention deficits. Nevertheless, all these drugs are extensively metabolized, have low plasma concentration, and cannot cross the blood–brain barrier freely. This review discusses different strategies for nanocarrier conjugation of these drugs for brain targeting and delivery, and new approaches on AD treatment according to the most accepted hypotheses of AD pathogenesis. Although none of the existent compounds or drugs can completely arrest the disease’s progression, nanocarrier development of anti-Alzheimer drugs could help delaying the initial or late stages of neurodegeneration. The discovery of new and more complex nanosystems with multiple approaches in AD treatment is needed and will be the next step in AD treatment in the near future.

Mechanism of NLRP3 inflammasome activation and its role in Alzheimer’s disease

Alzheimer’s disease (AD) is a common neurological disease in the elderly, and the major manifestations are cognitive dysfunction, neuronal loss, and neuropathic lesions in the brain. In the process of AD pathogenesis, the inflammatory response plays an indispensable role. The nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome containing NOD, leucine-rich repeat (LRR), and pyran domains is a multi-molecular complex that can detect dangerous signals related to neurological diseases. The assembly of NLRP3 inflammasome promotes the maturation of interleukin-1beta (IL-1β) and IL-18 mediated by caspase-1 in microglia, which leads to neuroinflammation and finally contributes to the occurrence and development of AD. This review aimed to clarify the structure and activating mechanism of NLRP3 inflammasome and its key role in the pathogenesis of AD, summarize the latest findings on the suppression of NLRP3 inflammasome activation for the treatment of AD, as well as indicate that targeting regulation of NLRP3 inflammasome assembly may be a potential strategy for the treatment of AD, providing a theoretical basis for the research of AD.

Research on Anti-Alzheimer’s Traditional Chinese Medicine with Data Security: Datasets, Methods, and Evaluation

Alzheimer’s disease (AD), a growing global health concern, has been posing a significant threat to the health of the aging population. The factors contributing to the occurrence and development of AD are extremely complex, including multiple neural networks and multiple targets, which join together to formulate enormous challenges in AD treatment. Traditional Chinese medicine (TCM) possesses the characteristics to regulate multiple targets at the same time, which is consistent with the pathogenesis of AD, moreover, clinical results in TCM treating AD reveal promising effects. In this paper, we first collected anti-Alzheimer’s prescriptions and their therapeutic effects from commonly used literature databases and expanded the data to form the anti-Alzheimer’s TCM dataset. Next, we combined machine learning models to train and analyze the dataset, which was used to predict the effectiveness of new TCM prescriptions. For the first time, we proposed to use the artificial intelligence method to train the properties of nature, flavor, and channel tropism in TCM prescriptions. The accuracy of the prediction model for the effectiveness of anti-Alzheimer’s can reach up to 85%. The experimental results demonstrated that our method can precisely predict the effectiveness of prescriptions against Alzheimer’s disease, and have great value in providing guidance for the development of new anti-Alzheimer’s drugs. Finally, we built a distributed model training architecture based on federated learning to train and predict the effectiveness of TCM prescriptions under the premise of ensuring data security.

Drug information of Aducanumab and its effectiveness for Alzheimer’s disease: A clinical review

Alzheimer’s disease (AD) is the main cause of disability in people older than 60 years. More than 1 million cases per year reported in India. AD and other kinds of dementia are more common as individuals become older, affecting 1 in every 14 people over the age of 65 and 1 in every 6 people over the age of 80. ADUHELM (Aducanumab) is a monoclonal antibody, new class of medication needed for treatment of AD. The latest drug used to treat underlying cause of AD and recent studies shown to be efficacious and safe for the AD. Our review emphasizes on the drug information of Aducanumab and its clinical importance in AD.

Effects of gut microbiota and probiotics on Alzheimer's disease.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with high morbidity, disability, and fatality rate, significantly increasing the global burden of public health. The failure in drug discovery over the past decades has stressed the urgency and importance of seeking new perspectives. Recently, gut microbiome (GM), with the ability to communicate with the brain bidirectionally through the microbiome–gut–brain axis, has attracted much attention in AD-related studies, owing to their strong associations with amyloids, systematic and focal inflammation, impairment of vascular homeostasis and gut barrier, mitochondrial dysfunction, etc., making the regulation of GM, specifically supplementation of probiotics a promising candidate for AD treatment. This article aims to review the leading-edge knowledge concerning potential roles of GM in AD pathogenesis and of probiotics in its treatment and prevention.

Screening for Core Genes Related to Pathogenesis of Alzheimer's Disease.

Alzheimer’s disease (AD), a nervous system disease, lacks effective therapies at present. RNA expression is the basic way to regulate life activities, and identifying related characteristics in AD patients may aid the exploration of AD pathogenesis and treatment. This study developed a classifier that could accurately classify AD patients and healthy people, and then obtained 3 core genes that may be related to the pathogenesis of AD. To this end, RNA expression data of the middle temporal gyrus of AD patients were firstly downloaded from GEO database, and the data were then normalized using limma package following a supplementation of missing data by k-Nearest Neighbor (KNN) algorithm. Afterwards, the top 500 genes of the most feature importance were obtained through Max-Relevance and Min-Redundancy (mRMR) analysis, and based on these genes, a series of AD classifiers were constructed through Support Vector Machine (SVM), Random Forest (RF), and KNN algorithms. Then, the KNN classifier with the highest Matthews correlation coefficient (MCC) value composed of 14 genes in incremental feature selection (IFS) analysis was identified as the best AD classifier. As analyzed, the 14 genes played a pivotal role in determination of AD and may be core genes associated with the pathogenesis of AD. Finally, protein-protein interaction (PPI) network and Random Walk with Restart (RWR) analysis were applied to obtain core gene-associated genes, and key pathways related to AD were further analyzed. Overall, this study contributed to a deeper understanding of AD pathogenesis and provided theoretical guidance for related research and experiments.

GLP-1 Receptor Agonist Inhibited the Activation of RIPK1 for Alleviation the Neuronal Death and Neuroinflammation in APP/PS1 Mice

Alzheimer’s disease (AD) is characterized by neuronal necroptosis and neuroinflammation, retardation of these pathological development was considered to play crucial role in the treatment of AD. RIPK1, a receptor-interacting serine/threonine-protein kinase 1, was reported to be involved in the mediation of neuronal necroptosis and neuroinflammation. Previous investigations indicated that the agonists of glucagon like peptide-1 receptor (GLP-1R) such as Liraglutide, showed ameliorating effect against the development of Alzheimer’s disease on model mice, however, the mechanisms by which GLP-1R agonists function in AD remains elusive. The effect of Liraglutide on the retardation of the AD progression upon regulation of RIPK1 was studied using biochemical and immune-histochemical assays in model mice. Results in this study ascertained that the GLP-1R agonists possessed inhibitory effect on RIPK1-mediated necroptosis and microglial activation in vitro and in vivo. It was evidenced that the utility of GLP-1R agonist is capable to reduce RIPK1 activity significantly and the effect of GLP-1R agonist showed PKA depended manner. This study clarified the relationship of GLP-1R agonist and RIPK1 and demonstrating the physiological effect of GLP-1R agonist in amelioration of AD. This study provided a mechanism underlying the function of GLP-1R agonist in AD and suggested a potential therapeutic strategies for the treatment of AD.

Dysregulated gene-associated biomarkers for Alzheimer's disease and aging.

Alzheimer’s disease (AD), the most common type of dementia, is a neurodegenerative disorder with a hidden onset, including difficult early detection and diagnosis. Nevertheless, the new crucial biomarkers for the diagnosis and pathogenesis of AD need to be explored further. Here, the common differentially expressed genes (DEGs) were identified through a comprehensive analysis of gene expression profiles from the Gene Expression Omnibus (GEO) database. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these DEGs were mainly associated with biological processes, cellular components, and molecular functions, which are involved in multiple cellular functions. Next, we found that 9 of the 24 genes showed the same regulatory changes in the blood of patients with AD compared to those in the GEO database, and 2 of the 24 genes showed a significant correlation with Montreal Cognitive Assessment scores. Finally, we determined that mice with AD and elderly mice had the same regulatory changes in the identified DEGs in both the blood and hippocampus. Our study identified several potential core biomarkers of AD and aging, which could contribute to the early detection, differential diagnosis, treatment, and pathological analysis of AD.

Molecular networking based dereplication of AChE inhibitory compounds from the medicinal plant Vincetoxicum funebre (Boiss. & Kotschy)

Alzheimer’s disease (AD) is a devastating neurodegenerative disease affecting 47 million people worldwide. While acetylcholinesterase (AChE) inhibitors such as donepezil and galantamine are leading drugs in the symptomatic treatment of AD, new AChE inhibitors continue to be explored for improved potency and selectivity. Herein, a molecular networking approach using high resolution (HR-MS) and tandem mass spectrometry (MS2) has been used for rapid chemical profiling of an extract of the medicinal plant Vincetoxicum funebre Boiss. & Kotschy (Apocynaceae family) that was active against AChE. A total of 44 compounds were identified by combining the MN with traditional natural product methods, including the isolation and identification of five known compounds (13, 41-44) and a novel C13-norisoprenoid (40). In addition, the potential inhibitory activity of all 44 compounds was evaluated against the AChE enzyme via molecular docking to provide further support to the proposed structures. The glycosylated flavonoid querciturone (31) exhibited the highest affinity with a docking score value of −13.43 kJ/mol. Another five compounds showed stronger docking scores against AChE than the clinically used donepezil including the most active isolated compound daucosterol (44), with a binding affinity of −10.11 kJ/mol towards AChE. These findings broaden our understanding of Vincetoxicum metabolites and highlight the potential of glycosylated flavonoids as AChE inhibitors. Communicated by Ramaswamy H. Sarma

Diabetic Theory in Anti-Alzheimer’s Drug Research and Development. Part 2: Therapeutic Potential of cAMP-Specific Phosphodiesterase Inhibitors

Alzheimer's disease (AD) is one of the most prevalent age-related neurodegenerative disease that affects the cognition, behavior, and daily activities of individuals. Studies indicate that this disease is characterized by several pathological mechanisms, including the accumulation of amyloid-beta peptide, hyperphosphorylation of tau protein, impairment of cholinergic neurotransmission, and increase in inflammatory responses within the central nervous system. Chronic neuroinflammation associated with AD is closely related to disturbances in metabolic processes, including insulin release and glucose metabolism. As AD is also called type III diabetes, diverse compounds having antidiabetic effects have been investigated as potential drugs for its symptomatic and disease-modifying treatment. In addition to insulin and oral antidiabetic drugs, scientific attention has been paid to cyclic-3',5'-adenosine monophosphate (cAMP)-specific phosphodiesterase (PDE) inhibitors that can modulate the concentration of glucose and related hormones and exert beneficial effects on memory, mood, and emotional processing. In this review, we present the most recent reports focusing on the involvement of cAMP-specific PDE4, PDE7, and PDE8 in glycemic and inflammatory response controls as well as the potential utility of the PDE inhibitors in the treatment of AD. Besides the results of in vitro and in vivo studies, the review also presents recent reports from clinical trials.

From Venom to AChE Inhibitor: Design, Molecular Modeling, and Synthesis of a Peptidic Inhibitor of AChE

Alzheimer’s disease (AD) is an irreversible and progressive brain disorder that slowly destroys memory and cognitive skills. The current treatment of AD mainly focused on the restoring of ACh levels through acetylcholinesterase (AChE) inhibition. Peptides are a unique class of pharmaceutical compounds that have privilege over small molecules, especially in the realm of protein–protein interactions and G protein-coupled receptor (GPCR) inhibitors. We applied a rational structure-based virtual design approach to discover new peptidic inhibitors of AChE. In this regard, conformational space in the fasciculin II (Fas) and AChE complex was evaluated utilizing MD simulation, principal component analysis and clustering to figure out possible interactions of Fas and AChE. Assessment of Fas–AChE interactions by visual evaluation and alanine scanning led to the design of 10 peptides. The highest scored peptide (p2) was selected and synthesized using SPPS. Based on Ellman's test, the inhibitory activity of p2 against AChE was 51.2 ± 8.1 µM. The kinetics study of the enzyme inhibition in accompany with molecular modeling results revealed that p2 was a mixed-type reversible inhibitor of AChE. The DNRMLRTTRY peptide was considerable inhibitor of AChE. Peptides have the merit of being big enough to inhibit PPI and GPCR class B with a wide binding site. But possible peptidic chemical space is too large to be evaluated by the classical peptide synthesis methods. In the present contribution, we introduced a rational in silico peptide design approach that led to the considerable peptidic inhibitor of AChE.

Malattia di Alzheimer: una storia antica in ottica moderna

Alzheimer’s disease (AD) involves impairment of the cognitive sphere, motor skills and higher functions, progressive deconstruction of the mind-body system and loss of autonomy. The brain with AD shows extracellular amyloid-β plaques, intraneuronal tangles of hyperphosphorylated tau, and inflammation. The article presents the pathogenesis, the possible prevention and treatment of AD according to the Pnei paradigm: modifiable and unchangeable risk factors are known. Among the formers, a preventive role is assigned to certain behaviors: a correct diet, regular physical activity, the maintenance of significant interpersonal bonds, the control of cardiovascular risk, protection from psychoemotional stress, early treatment of depression and abstention from alcohol and tobacco. The Pnei approach guarantees a systemic look at the clinical-metabolic manifestations of AD (disease), the patient’s experience of illness (illness) and the possibility of residual autonomy (sickness). At present, the study courses on AD created by multidisciplinary teams of professionals, integrated with each other, are increasingly valid.

Pharmacophore-driven identification of N-methyl-D-receptor antagonists as potent neuroprotective agents validated using in vivo studies.

Alzheimer’s disease (AD), apparently the most widespread reason behind dementia, is delineated by a continuous cognitive weakening in the aged. During its progression, N-methyl-D-aspartate receptor (NMDAR) antagonists are known to play a pivotal part in the mechanisms of learning and memory. Since there is an unmet medical need for the treatment of AD, we aim to identify possible chemical compounds targeted toward N-methyl-D-aspartate receptors. Three-dimensional models are developed to unveil some of the essential characteristics of the N-methyl-D-aspartate receptors by using a collection of already discovered N-methyl-D-aspartate receptor inhibitors. This is followed by virtual screening, which results in novel chemical compounds having the potential to inhibit N-methyl-D-aspartate receptors. Molecular docking studies and analysis promulgated two lead compounds with a high LibDock score. The compounds are shortlisted based on high estimated activity, fit values, LibDock score, no violation of Lipinski’s, and availability for procuring. Finally, the shortlisted compounds are tested by employing in vivo studies, which we further propose as potential NMDA inhibitors for treating AD.

The use of Huperzia species for the treatment of Alzheimer's disease.

Alzheimer's disease (AD), which relates to nervous degeneration, is the most popular form of memory loss. The pathogenesis of AD is not fully understood, and there are no therapies for this disorder. Some drugs have been used in clinical applications for preventing and treating AD, but they have significant adverse reactions. Therefore, there is a need to develop treatment for AD. Traditional medicine has used many medicinal plants to alleviate the symptoms of AD. Medicinal plants may reduce neurodegenerative disorders with fewer side effects than chemical drugs, and they are promising drug candidates for AD therapy. This review is the summary of the pathogenesis and treatments of AD and includes information about the chemistry and bioactivities of some medicinal plants from the Huperzia species, such as Huperzia saururus, Huperzia selago, Huperzia phlegmaria, Huperzia fargesii, Huperzia serrata, Huperzia reflexa and Huperzia quadrifariata, that are used for the treatment of AD. We searched literature, including Medline, Embase, Google Scholar and PubMed database, and did a bibliographic review of relevant articles. Key words included Huperzia species, huperzine, huperin, Huperzia and Alzheimer's disease. We found that the main bioactive compounds of the Huperzia species are alkaloids, which have shown significant effects on preventing the development of AD. They are new promising compounds against AD due to their antioxidant, anti-inflammatory and acetylcholinesterase inhibitory activities in the neural system. Our conclusion from this review is that the Huperzia species are potential source containing various pharmaceutical compounds for the treatment of AD.

Reappraisal of FDA approved drugs against Alzheimer’s disease based on differential gene expression and protein interaction network analysis: an in silico approach

Alzheimer’s disease (AD), a most prevailing neurodegenerative disorder with turbulence in cognitive and behavioural abilities, epitomizes one of the highest unmet medical requirements. The current AD treatment focuses merely on symptomatic relief, this explains a dearth in drug research oriented towards unwinding of disease specific druggable targets. On the other hand, toxicity and poor bioavailability hamper the evolution of novel chemical entities (NCE) in clinical trials. Drug repurposing offers a gateway to rejuvenate new therapeutic applications for existing approved drugs. This study concentrates on the identification of potential druggable AD targets and screening of FDA approved drugs with a concept of drug repurposing. differentially expressed genes (DEGs) were identified in frontal cortex, temporal cortex and hippocampus in AD patients from Gene Expression Omnibus (GEO) dataset GSE36980. Protein-protein interaction (PPI) analysis revealed SERPINA3 and BDNF to possess high node degree interaction with literature derived candidate genes (LDGs) in AD males and females, respectively, thus were selected as potential AD targets. Subsequently, FDA approved drugs were screened through the above shortlisted targets and were ranked based on molecular docking and MM-GBSA energy calculations using Glide and Prime tools, respectively. Drugs possessing best docking score and maximum binding energy were further evaluated through molecular dynamics simulation studies, which revealed the affinity of Tiludronic acid and Olsalazine towards SERPINA3 and BDNF, respectively.

Interaction of synthesized nitrogen enriched graphene quantum dots with novel anti-Alzheimer’s drugs: spectroscopic insights

Alzheimer’s disease (AD) is considered as one of widespread dementia with no approved diagnosis, cure or prevention. Currently, only symptomatic relief can be provided upon administration of anti-AD drugs generally belonging to a category of anticholinesterases and antagonists of N-methyl-D-aspartate (NMDA) receptors. In present investigation, a sensing platform has been designed for studying recently developed anti-AD drugs viz., PC-25 (N-(2-{4-[(4-bromophenyl)methyl]piperazin-1-yl}ethyl)-7-methoxy-1,2,3,4-tetrahydroacridin-9-amine trihydrochloride), PC-37 (7-methoxy-N-(2-{4-[(3-methylphenyl)methyl]piperazin-1-yl}ethyl)-1,2,3,4-tetrahydroacridin-9-amine trihydrochloride) and PC-48 (N-(2-{4-[(3-bromophenyl) methyl]piperazin-1-yl}ethyl)-7-methoxy-1,2,3,4-tetrahydroacridin-9-amine trihydrochloride) and two known standard tacrine (THA) and donepezil drugs for their estimation of in vitro potency towards AD using spectroscopic method. Anti-AD drugs have been accounted for individually with highly fluorescent nitrogen-doped graphene quantum dots (NGQDs). The designed anti-AD drugs exerted the efficacy related to cholinergic hypothesis of AD. While the enzyme action is sensed by interacted species of NGQDs and acetylcholine, the fluorescence of NGQDs is quenched by the hydrolyzing action of acetylcholinesterase (AChE) enzyme but the lost fluorescence is recovered upon addition of anti-AD drugs. These alterations in fluorescence of NGQDs are expected to have biological relevance akin to sensing. Moreover, these results advocate that out of all the drugs tested PC-37 displayed maximum inhibition efficiency. Our investigations suggest that synthesized drugs have the AD treating potential and can be entrusted in the near future for AD treatment. The validation parameters such as LOD, LOQ and recovery (%) were calculated in the range of 2.87 mM, 9.58 mM and 85–96%, respectively.Communicated by Ramaswamy H. Sarma

Molecular Markers of Early Diagnosis of Alzheimer Disease: Prospects for Research in Peripheral Tissues

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder of elderly and old-aged people. Cerebrospinal fluid (CSF) and peripheral tissues—lymphocytes and platelets, buccal and olfactory epithelium, and skin fibroblasts—are used for intravital diagnostics of the expression of signaling molecules (AD markers). There are several changes in the production of hyperphosphorylated τ-protein form, BACE1, and peptide Aβ42 in CSF in the case of AD, but CSF sampling can have a number of side effects. Biopsies of the epithelium and portions of blood are a less traumatic method of obtaining tissue samples for AD diagnosis. An increase in the expression of the hyperphosphorylated form of τ-protein is shown in the blood lymphocytes of AD patients. An increase in the content of high molecular forms of phosphorylated τ protein and amyloid precursor protein (APP) was also detected in the platelets of AD patients. Changes in the amount of two miRNA families, miR-132 and miR-134, were detected in blood cells 1–5 years before the manifestation of clinical signs of AD. An increase in the bound-calcium concentration, Aβ40 and Aβ42 peptide synthesis, and τ protein was observed in AD skin fibroblasts. In olfactory and buccal epithelia, an increase in the expression of hyperphosphorylated τ-protein form and Aβ peptide was detected in AD patients. The detection of AD markers in peripheral tissues available for biopsy is highly important for intravital diagnostics, prevention, and targeted treatment of AD.

The Use of Anti-Diabetic Drugs in Alzheimer’s Disease, New Therapeutic Options and Future Perspective

Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by progressive loss of memory, confusion, inability of speech and decline in the cognitive behavior. It is considered one of the most common forms of dementia. Clinical studies and preclinical data in the last decade proved that AD and Diabetes mellitus share a pathophysiological pathway, indicating that insulin resistance, oxidative stress and inflammatory response would increase the risks of developing AD in diabetic patients. This review presents briefly the etiology of AD and Diabetes, discusses the possible theories about the interplaying risk factors and the mechanism of action of anti-diabetic medications recommended for the treatment of AD. It is concluded that antidiabetics have good potential to improve dementia, especially in earlier AD stages. However, many of the underlying intricate molecular pathways are still unclear and thus thorough future research is required.

Medicinal Plants Anti-cholinesterase Activity and the Potential for Alzheimer’s Disease Treatment

Alzheimer’s disease (AD) is a slow and progressive neurodegenerative disease, leading to a breakdown in memory preservation and absence of cognitive reasoning and language skills. It is the most popular neurodegenerative disease worldwide, with nearly 20 million new incidences recorded every year. The enzymes, acetyl cholinesterase (AChE) and butyryl-cholinesterase (BChE) play important roles in the cholinergic deficit through enhanced degradation of the neurotransmitter, acetylcholine (ACh). In most cases, to improve neurotransmission and to alleviate cholinergic deficit, the focus is mainly on acetyl cholinesterase (AChE) and butyl cholinesterase (BCh). Currently, drugs for the treatment of AD (Rivastigmine, galanthamine, donepezil and Memantine) targets the later stages and implicated in the progression of the disease. Acetyl cholinesterase enzyme (AChE) is especially an attractive target for the rational drug design and for the discovery of mechanism based inhibitors; this is because of its role in the hydrolysis of neurotransmitter, acetylcholine. Many plants serve as potential source of AChE and BChE inhibitors, and useful compounds that could provide templates for the development of drugs for the treatment of AD. This paper provides a review of several medicinal plants tested for anti-AChE and or BChE, many of which contains promising bioactive compounds as potential anti-cholinesterase that could serve as candidates for the development of drugs to treat AD.

Combinatorial Vaccine against Complement Factor C5a and Amyloid Beta: A New Therapeutic Approach in Alzheimers Disease

Alzheimer’s disease (AD) is the most common neurodegenerative disease characterized by neuronal loss due to amyloid beta (Aβ) aggregations, neurofibrillary tangles, and prominent neuroinflammation. Inflammatory processes in AD primarily occur in response to misfolded and aggregated proteins, or mislocalized nucleic acids and reactive microglia. Prolonged chronic neuroinflammation is thought to reinforce neuronal cell dysfunction and cell death. In our previous study we demonstrated that the interference with the pro-inflammatory mediator C5a by AFF1 vaccine at an early stage of disease is able to reduce microglia activation and amyloid plaque burden which is accompanied by ameliorated memory deficiency in Tg2576 mice, a mouse model of AD. In a follow-up study we tested the effect of a combinatorial vaccine targeting neuroinflammation by C5a and Aβ aggregates, two detrimental processes in AD. The amyloid plaque burden in the brain of Tg2576 mice was significantly reduced upon vaccination by the monovalent anti-C5a (AFF1) as well as anti-Aβ (AD02) vaccine, however, the combinatorial AFF1/AD02 vaccine showed a clear additive beneficial effect. Moreover, contextual memory in Tg2576 mice was significantly improved by the combinatorial AFF1/AD02 vaccine when compared to monovalent or control vaccines. Thus, targeting two neuropathological processes such as neuroinflammation and Aβ aggregation may represent a new and promising approach for the treatment of AD.