AbstractAlzheimer’s Disease Progression Research Articles

A MECHANISM OF ACTION OF HUMAN-ORIGIN PROBIOTIC COCKTAIL IN ATTENUATING ALZHEIMER’S DISEASE PATHOLOGY

Abstract Alzheimer’s disease (AD) is a detrimental public health problem affecting millions of older adults in the USA alone, with no or limited treatment options. Emerging evidence indicates the pivotal role of gut microbiota in AD pathology, but mechanisms remain largely unknown. Also, microbiome modulators like probiotics are proven beneficial in preventing AD with little understanding of their mechanisms. Therefore, we investigated how a microbiota metabolite-short-chain free fatty acid receptor-2 (FFAR2) signaling in the intestine affects AD pathology in brain using intestinal FFAR2 knock-out APP/PS-1 mice; as well as determined if a human-origin-probiotic cocktail exhibits its actions via FFAR2 signaling. We measured changes in the microbiome, permeability in gut and blood-brain barriers (BBB), neuroinflammation, AD pathology, and cognitive behaviors. Results showed, the mice lacking FFAR2 in their intestine exacerbated AD pathology by developing abnormal changes in gut microbiome and intestinal permeability, which in turn promotes permeability in BBB and neuroinflammation. It’s also promoting microglia activation linked with increased Aβ accumulation and cognitive decline. It’s interesting to note that probiotic cocktail feeding reversed these abnormalities in AD mouse models. Further, this probiotic cocktail showed its mechanism in both FFAR2-dependent and independent manner. Overall, our findings indicate that the microbiome sensing mechanism FFAR2 signaling participates in regulating the gut-brain in AD pathology, and a human-origin probiotic cocktail improves the abnormal changes in the microbiome-intestinal & BBB permeability-neuroinflammation axis to ameliorate AD pathology. Thus, FFAR2 agonism and probiotic therapy can be viable options to prevent/ delay the risk of AD progression in older adults.

The elusive role of herpesviruses in Alzheimer's disease: current evidence and future directions.

Alzheimer's disease (AD) is the most common cause of dementia. While pathologic hallmarks, such as extracellular beta-amyloid plaques, are well-characterized in affected individuals, the pathogenesis that causes plaque formation and eventual cognitive decline is not well understood. A recent resurgence of the decades-old "infectious hypothesis" has garnered increased attention on the potential role that microbes may play in AD. In this theory, it is thought that pathogens such as viruses may act as seeds for beta-amyloid aggregation, ultimately leading to plaques. Interest in the infectious hypothesis has also spurred further investigation into additional characteristics of viral infection that may play a role in AD progression, such as neuroinflammation, latency, and viral DNA integration. While a flurry of research in this area has been recently published, with herpesviruses being of particular interest, the role of pathogens in AD remains controversial. In this review, the insights gained thus far into the possible role of herpesviruses in AD are summarized. The challenges and potential future directions of herpesvirus research in AD and dementia are also discussed.

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.

Characterization of the transcriptome and TCR of brain and cerebrospinal fluid infiltrated CD8 +T cells in an Alzheimer’s disease mouse model

Abstract Alzheimer’s disease (AD) is a common form of dementia characterized by the accumulation of protein aggregates in the brain of older adults. It has been observed that CD8 +T cells, particularly CD8 +TEMRA cells, infiltrate the brain and cerebrospinal fluid (CSF) of AD patients. However, the precise role of these cells in the development and progression of AD is not well understood. In this study, we used single-cell RNA sequencing (scRNAseq) and single-cell T cell receptor sequencing (scTCRseq) to examine the CD8 +T cells in the brain and CSF of a mouse model of AD (5xFAD) and its wild-type (WT) littermate controls. The AD mice (age 40–70 weeks) used in our experiments have developed memory deficits. Our analysis revealed a significant increase in the number of CD8 +T cells in the brain and CSF of AD mice compared to WT controls (n=4, p<0.05). Furthermore, these cells displayed a distinct transcriptome profile characterized by increased expression of inflammatory pathways, compared to WT mice. Through TCR sequence analysis, we also observed significant clonal expansion of CD8 +T cells in AD mice compared to WT mice. These findings provide a starting point for further investigation into the role of infiltrating CD8 +T cells in the pathogenesis of AD in this mouse model.

Continued food allergen consumption exacerbates beta-amyloid accumulation in allergen-sensitized App NL-G-Fmice

Abstract Alzheimer’s disease (AD) is the most common neurodegenerative disease, with β-amyloid (Aβ) plaque deposition being one of the hallmark pathologies. However, the etiology of AD remains elusive. While chronic inflammation from recurrent infections or injury seems to contribute to AD development, it is unclear whether atopic diseases, such as allergies, are associated with AD. We previously reported that continuous consumption of a whey protein (WP)-containing diet led to lasting neuroinflammation in C57BL/6J mice that were sensitized but tolerant to a bovine milk allergen, β-lactoglobulin (BLG; Bos d 5). Thus, we hypothesized that the persisting neuroinflammation due to repeated allergen consumption would exacerbate AD pathology over time in genetically predisposed, allergen-tolerant individuals. To address this hypothesis, we sensitized 1-month-old male and female transgenic App NL-G-Fknock-in mice to BLG and subsequently fed them either a whey-free control or a WP diet for 6 months. Despite their lack of overt allergic reactions, BLG-sensitized mice showed elevated plasma levels of BLG-specific IgE and IgG1. Leukocyte infiltration was observed in the hippocampus of sensitized mice, and WP-fed sham mice to a lesser extent. In contrast, mast cell accumulation was apparent in the dura of sensitized mice regardless of the diet. Importantly, Aβ plaque load and Aβ peptide levels were greater in the hippocampus of BLG-sensitized mice on the WP diet compared to the respective sham group. These results indicated that continuous allergen consumption exacerbated AD-like pathology in BLG-sensitized App NL-G-Fmice, suggesting that chronic food allergen exposure may promote the progression of AD in susceptible individuals. Supported by the National Institute of Health/National Institute on Aging (NIH/NIA) under grant number R21AG070412

Diterpenoid Caesalmin C Delays Aβ-Induced Paralysis Symptoms via the DAF-16 Pathway in Caenorhabditis elegans.

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease in the world. However, there is no effective drug to cure it. Caesalmin C is a cassane-type diterpenoid abundant in Caesalpinia bonduc (Linn.) Roxb. In this study, we investigated the effect of caesalmin C on Aβ-induced toxicity and possible mechanisms in the transgenic Caenorhabditis elegans AD model. Our results showed that caesalmin C significantly alleviated the Aβ-induced paralysis phenotype in transgenic CL4176 strain C. elegans. Caesalmin C dramatically reduced the content of Aβ monomers, oligomers, and deposited spots in AD C. elegans. In addition, mRNA levels of sod-3, gst-4, and rpt-3 were up-regulated, and mRNA levels of ace-1 were down-regulated in nematodes treated with caesalmin C. The results of the RNAi assay showed that the inhibitory effect of caesalmin C on the nematode paralysis phenotype required the DAF-16 signaling pathway, but not SKN-1 and HSF-1. Further evidence suggested that caesalmin C may also have the effect of inhibiting acetylcholinesterase (AchE) and upregulating proteasome activity. These findings suggest that caesalmin C delays the progression of AD in C. elegans via the DAF-16 signaling pathway and that it could be developed into a promising medication to treat AD.

Effects of DISC1 on Alzheimer's disease cell models assessed by iTRAQ proteomics analysis.

Alzheimer’s disease (AD) is a form of neurodegenerative disease in the elderly with no cure at present. In a previous study, we found that the scaffold protein, disrupted in Schizophrenia 1 (DISC1) is down-regulated in the AD brains, and ectopic expression of DISC1 can delay the progression of AD by protecting synaptic plasticity and down-regulating BACE1. However, the underlying mechanisms remain not to be elucidated. In the present study, we compared the proteomes of normal and DISC1high AD cells expressing the amyloid precursor protein (APP) using isobaric tag for relative and absolute quantitation (iTRAQ) and mass spectrometry (MS). The differentially expressed proteins (DEPs) were identified, and the protein–protein interaction (PPI) network was constructed to identify the interacting partners of DISC1. Based on the interaction scores, NDE1, GRM3, PTGER3 and KATNA1 were identified as functionally or physically related to DISC1, and may therefore regulate AD development. The DEPs were functionally annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases with the DAVID software, and the Non-supervised Orthologous Groups (eggNOG) database was used to determine their evolutionary relationships. The DEPs were significantly enriched in microtubules and mitochondria-related pathways. Gene set enrichment analysis (GSEA) was performed to identify genes and pathways that are activated when DISC1 is overexpressed. Our findings provide novel insights into the regulatory mechanisms underlying DISC1 function in AD.

The Therapeutic Potential of Synthetic and Natural Cannabinoids in Treating Alzheimer’s Disease

Alzheimer’s disease (AD) is one of the most prevalent and debilitating neurodegenerative diseases in the world, highlighting the need for research on novel treatments and therapies. Previous studies have found that the body’s endocannabinoid system (ECS) interacts closely with its neural system, making it a potential avenue for the treatment of neurological disorders. One hallmark of AD is the accumulation of amyloid-beta (Aβ) in the brain and its potentially detrimental effects on cognitive function. Cannabis-based drugs have been observed to regulate Aβ modifications and inhibit AD progression. Furthermore, cannabinoids have been noted to reduce inflammation and neurotoxicity. Synthetic cannabinoids were able to rescue memory deficits and neurodegeneration, and reduce immunoreactivity. Similarly, natural cannabinoids like Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) demonstrate therapeutic potential by interacting with the cholinergic system, and reversing the symptoms of AD. Although further research and testing are needed, it is evident that the use of cannabinoids shows promise for future treatment in AD patients.

Mitochondrial Dysfunction in Alzheimer’s Disease and Possible Therapeutic Targets to Prevent Progression of Alzheimer’s Disease

Alzheimer’s Disease (AD) is the most frequent cause of dementia in aged population. Till now, there is no effective treatment for AD. Now various studies have kinked AD to mitochondrial dysfunction, due to accumulation of Aβaggregates, neurofibrillary tangles, cholinergic transmission, oxidative stress and neuroinflammation causing neurodegeneration and cognitive decline seen in AD. Here in this article, how the mitochondrial dysfunction/dynamics are involved in the pathogenesis of cognitive decline seen in cases of AD and various therapeutics targeted against mitochondrial dysfunctions are described, thereby causing a ray of hope for preventing progression of AD.

MiR-485-5p alleviates Alzheimer's disease progression by targeting PACS1.

Alzheimer’s disease (AD) is a common dementia and a heterogeneous disease. Previous research has validated that microRNAs (miRNAs) are pivotal regulators in the initiation and development of tremendous diseases including AD. MicroRNA-485-5p (miR-485-5p) was reported to be an important participant implicated in several neurological diseases, but its role in AD still needs to be further investigated. In this research, we explored the biological function of miR-485-5p in AD. RT-qPCR revealed that miR-485-5p expression was downregulated in the hippocampus of APP/PS1 mice. Additionally, miR-485-5p overexpression facilitated the learning and memory capabilities of APP/PS1 mice according to Morris water maze test, fear conditioning test, and immunofluorescent staining. Moreover, CCK-8 assay, flow cytometric analysis, and western blot analysis suggested that miR-485-5p overexpression promoted pericyte viability and prohibited pericyte apoptosis in APP/PS1 mice. Mechanistically, miR-485-5p directly targeted PACS1 in pericytes, as shown in a luciferase reporter assay. In rescue assays, PACS1 overexpression countervailed the effect of miR-485-5p overexpression on pericyte viability and apoptosis. In conclusion, miR-485-5p ameliorates AD progression by targeting PACS1.

Uncal apex movement and positioning in Alzheimer's Disease

Alzheimer’s Disease (AD) patients have consistently shown declines in declarative memory, consolidation, and in many other cognitive areas. These changes are associated with atrophy and volumetric declines in medial temporal lobe structures, such as the hippocampus. Hippocampal atrophy has been associated with AD. However, the influence of AD atrophy on the position of the uncal apex—an anatomical landmark for the hippocampus—has not been longitudinally examined. The current study’s objective is to investigate changes in the position of the uncal apex of AD patients over the course of two years. The current study draws upon the Alzheimer’s Disease Neuroimaging Initiative (ADNI) data set (adni.loni.usc.edu). For each participant, I obtained demographic data, anatomical MRI images in native space, hippocampal segmentations from the subcortical stream of FreeSurfer (v.5.3.0), and linear transforms to MNI space. Using uncal apex y-positions transformed in MNI space, I found that the uncal apex fell in a more posterior position in AD patients relative to control and that over time, the uncal apex migrates toward a more anterior position in both groups. These results suggest that part of the neuroimaging examinations that are done on AD patients should examine uncal apex positions as a biomarker of early AD progression. Future directions and limitations are discussed

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.

Nowe strategie terapeutyczne choroby Alzheimera

Streszczenie Choroba Alzheimera (AD, Alzheimer’s disease) opisywana jako przewlekłe i nieodwracalne schorzenie neurodegeneracyjne pozostaje najczęstszą przyczyną demencji. Ze względu na obserwowane od dłuższego czasu zjawisko starzenia się populacji, nieuleczalność AD stała się narastającym problem medycyny XXI w. Obecne metody leczenia mają wyłącznie charakter objawowy, zapewniają minimalne, czasowe usprawnienie funkcji poznawczych pacjentów. W pracy przedstawiono najnowsze kierunki poszukiwań skutecznej farmakoterapii zdolnej do zapobieżenia lub zahamowania progresji AD. Ze względu na to, iż nie jest znana dokładna patogeneza choroby Alzheimera główne strategie terapeutyczne opierają się jedynie na hipotezach: kaskady amyloidowej, białka tau, stresu oksydacyjnego, neurozapalenia oraz tych związanych z dysfunkcją układu cholinergicznego, jak również glutaminianergicznego. Większość związków obecnie testowanych w badaniach klinicznych nakierowana jest na patologiczny amyloid β (Aβ), będący narzędziem sprawczym neurodegeneracji, według opisywanej dotychczas najszerzej teorii kaskady amyloidowej. Z toksycznym Aβ próbuje się walczyć za pośrednictwem: immunoterapii (szczepionki, przeciwciała monoklonalne), związków hamujących jego powstanie: inhibitorów/modulatorów γ-sekretazy i inhibitorów β-sekretazy. Immunoterapię próbuje się wykorzystać również do nasilenia klirensu hiperfosforylowanego białka tau, którego obecność jest nieodzowną cechą choroby Alzheimera. Oprócz przedstawicieli immunoterapii, przedmiotem prac badawczych stały się również związki o działaniu przeciwzapalnym, metabolicznym i neuroprotekcyjnym. W fazę badań klinicznych zostały wprowadzone ponadto związki działające objawowo, które wyrównując deficyty cholinergiczne, noradrenergiczne i glutaminianergiczne poprawiają funkcje poznawcze.

Down-regulation of SORL1 is associated with Alzheimer's disease through activating ABC transporter pathway.

Alzheimer's disease (AD) is a common neurodegenerative disease with high morbidity among elderly people. A genetic attribution has been extensively proved. Here, we propose to further prioritize genes that harbor single nucleotide variation (SNV) or structural variation (SV) for AD and explore the underlying potential mechanisms through exploiting their expression and methylation spectra. A high-confidence AD-associated candidate gene list was obtained from the ClinVar and Human Gene Mutation Database (HGMD). Genome-wide methylation and expression profiles of AD and normal subjects were downloaded from the Gene Expression Omnibus (GEO). Through comprehensive comparison of expression and methylation levels between AD and normal samples, as well as different stages of AD samples, SORL1 was identified as the most plausible gene for AD incidence and progression. Gene Set Enrichment Analysis (GSEA) revealed significant activation of the ABC (ATP binding cassette) transporter with the aberrant up-regulation of SORL1 within AD samples. This study unfolds the expression and methylation spectra of previously probed genes with SNV or SV in AD for the first time, and reports an aberrant activation of the ABC transporter pathway that might contribute to AD progression. This should shed some light on AD diagnosis and precision treatment.

Exosome-encapsulated microRNAs as promising biomarkers for Alzheimer's disease.

Alzheimer's disease (AD) is a chronic neurodegenerative disease that locks into long clinical latency and low curative ratio. Therefore, early diagnosis before the clinical phase is quite essential and may be effective for therapeutic prevention. Peripheral blood or cerebrospinal fluid biomarkers symbolizing functional neuronal impairment are gradually applied to diagnose AD in research studies. Exosomes have generated immense interest in the diagnosis field of neurodegenerative disorders after confirmation of their roles as mediators, delivering important proteins and microRNAs (miRNAs) in intercellular communication. Compelling research results reveal that miRNAs released from exosomes modulate expression and function of amyloid precursor proteins and tau proteins. These findings open up possibility that dysfunctional exosomal miRNAs may influence AD progression. In this review, we summarized the existing knowledge of exosomal miRNAs and their involvement in AD, emphasizing their potential to serve as diagnostic biomarkers during the preclinical phase of AD.

Differential effects of NSAIDs on amyloid β1-42 peptide aggregation

Alzheimer’s disease (AD) is the most common cause of dementia and one of the great health-care challenges of the 21st century. The disease is characterised by extracellular aggregation of the amyloid beta (Aβ1-42) peptide within the brain, with subsequent formation of plaques leading to dementia. Currently, there is no cure for AD with only symptomatic therapies available which have demonstrated no, or limited, efficacy. Current pharmacologic studies into AD have focused principally on the development of disease-modifying therapies that can slow the progression of AD. Targets of these investigational agents include Aβ1-42 production, aggregation, and clearance. The ability of non-steroidal anti-inflammatory drugs (NSAIDs) to influence Aβ1-42 aggregation was assessed using the thioflavin-T spectrofluorimetric assay. Mefenamic acid and flufenamic acid both significantly reduced Aβ1-42 aggregation in vitro; however ibuprofen and naproxen had no significant effect on aggregation. These studies highlight that NSAIDs may have potential for helping manage or treat AD.

Identification of Peripheral Immune Mechanisms playing a protective role in Alzheimer's Disease progression

Abstract Alzheimer’s disease (AD) has become the most common form of dementia in the elderly. Recent studies have highlighted the role of inflammation and the immune system in the etiology of AD. However, there is a key gap in knowledge regarding the immune processes in healthy aged individuals as compared to AD patients. We have recently demonstrated that healthy aged subjects display a weak immune/inflammatory response to Amyloid beta–Aβ peptide (1–42) characterized by high IgM antibody responses. In contrast, MCI or AD patients exhibit high levels of IgG antibody against Aβ indicative of a strong immune response. IL-21, an inflammatory cytokine that enhances the differentiation of B cells and facilitates the class switching of IgM to IgG antibodies, is also upregulated in the plasma of AD patients compared to healthy aged controls. In support of these human data, our pre-clinical in vivo experiments using the 5xFAD mouse model of AD also display increased immune activation as compared to age-matched control mice. Similar to humans, we observed a decreased IgM and increased IgG response against Aβ. Furthermore the increased IgM antibody response correlated negatively with cognitive dysfunction. In addition, we also observed an increase in the proportions of T follicular helper (Tfh) cells which secrete IL-21, and enhance the B cell class switch to IgG antibodies in AD mice. In summary, our data indicate that weak immune/inflammatory response against Aβ is protective and facilitates the clearance of Aβ without inducing damaging levels of inflammation. In contrast, strong immune/inflammatory response against Aβ such as those observed in MCI and AD subjects and mice enhance inflammation and aid AD progression.

ID2016 Human mesenchymal stem cell derived model of Alzheimer’s disease – effect of Wnt antagonism in neurodegeneration

Alzheimer’s disease (AD), one of the most common types of dementia, is a serious and increasing health problem. This progressive disorder is manifested by loss of memory which worsens over time. Although several causative mechanisms for AD has been identified, the specific molecular mechanisms for the onset and progression of the disease has not yet been elucidated. This is mainly because of the lack of patient tissue at various stages of disease, in order to test and ascertain the molecular progression of AD. To address this lacuna, we have developed a human stem cell model of AD, derived from mesenchymal stem cells (MSCs) of perinatal tissues. We first derived cells of the central nervous system (CNS) from MSCs and then subjected them to AD specific neurodegeneration. Onset of neurodegeneration was ascertained by accumulation of BACE, nAChAR and presenilin. Neuronal generation was first established for expression neuronal specific markers such as nestin, Tuj1, Pax6, Sox1 and 2 by immunocytochemistry and quantitative RT-PCR. In the AD model thus established, we analysed further for the role of Wnt antagonists, sFRP3 and 4 and deciphered a link between inhibition of the Wnt-b catenin pathway and the onset of neurodegeneration. These studies would pave the way for the development of specific biomarkers for progression of AD and novel drug targets based on these biomarkers

Cargo trafficking in Alzheimer’s disease: the possible role of retromer.

Alzheimer’s disease (AD) as one of the on going neurological disorders is initiated and progressed by multiple pathological pathways. Cargoes trafficking pathways,such as recycling, play a crucial role in the pathogenesis of AD. One of the major constituents of this trafficking system in neurons is retromer which acts in endosomal sorting machinery. Defective retromer disrupts recycling of cargoes from endosomes to Golgi and leads to its mis-trafficking which may subsequently leads to AD. Also, retromer-related cargo trafficking could trigger amyloidogenic pathway and beta-amyloid production. Wingless is another cargo in Wnt pathways and its trafficking is mediated by retromer. Retromer malfunction leads to lack of Wnt and subsequent AD-related pathogenesis. Also, retromer plays role in synaptic receptor trafficking in physiologic and pathologic conditions. This review is brief survey on the recent published literatures about pathogenesis of retromer-related trafficking in amyloid precursor protein pathways, Wnt signaling, synaptic function, and also revised the structural role of retromer in AD progression.

Characterization of inflammatory biomarkers and candidates for diagnosis of Alzheimer’s disease

Alzheimer’s disease (AD) is the most common form of neurodegenerative dementia, several genetic, non-genetic, and environmental factors could be involved in disease progression. Association was suggested between inflammation and AD progression. Since neuroinflammation can be involved in neurodegeneration, studies suggested that several inflammatory molecules (cytokines) might enhance the inflammation or suppress the immune system. Altered cytokine levels might reflect the neuropathological changes in patients. This review summarizes the validated and potential inflammatory biomarkers in AD, and it is focusing on interleukins (ILs), interferons (IFNs) and tumor necrosis factors (TNFs). Interleukins have dual role in the AD progression: Several ILs (such as IL1, IL6 or IL8) can promote the disease-associated inflammatory pathways, while the others (such as IL1ra, IL4 or IL10) might be involved in the neuroprotection and dementia prevention. Conflicting reports are available on the role of IFNs (IFNα, IFNβ and IFNγ) in AD progression. Several studies reported that they might have neuroprotective effects, but the others suggested that they can contribute to neurotoxiciy by inducing the pro-inflammatory cytokines. TNFα can be expressed with other pro-inflammatory cytokines and induce the neurodegeneration. Both TNFα and TNFR were suggested as successful markers for AD and dementia. Several cytokines can be used to distinguish the AD patients from the healthy individuals, since their expression might be up-or down-regulated in the brain of AD patients. Some cytokines might be useful to measure the severity of the disorder. Overproduction of pro-inflammatory molecules could result neuroinflammation and enhance the neurotoxicity. Inhibiting the pro-inflammatory- and/ or inducing the anti-inflammatory molecules might improve the therapies for AD.