The SMXL8-AGL9 module mediates crosstalk between strigolactone and gibberellin to regulate strigolactone-induced anthocyanin biosynthesis in apple.

Although the strigolactone (SL) signaling pathway and SL-mediated anthocyanin biosynthesis have been reported, the molecular association between SL signaling and anthocyanin biosynthesis remains unclear. In this study, we identified the SL signal transduction pathway associated with anthocyanin biosynthesis and the crosstalk between gibberellin (GA) and SL signaling in apple (Malus × domestica). ELONGATED HYPOCOTYL5 (HY5) acts as a key node integrating SL signaling and anthocyanin biosynthesis, and the SL response factor AGAMOUS-LIKE MADS-BOX9 (AGL9) promotes anthocyanin biosynthesis by activating HY5 transcription. The SL signaling repressor SUPPRESSOR OF MAX2 1-LIKE8 (SMXL8) interacts with AGL9 to form a complex that inhibits anthocyanin biosynthesis by downregulating HY5 expression. Moreover, the E3 ubiquitin ligase PROTEOLYSIS1 (PRT1) mediates the ubiquitination-mediated degradation of SMXL8, which is a key part of the SL signal transduction pathway associated with anthocyanin biosynthesis. In addition, the GA signaling repressor REPRESSOR-of-ga1-3-LIKE2a (RGL2a) mediates the crosstalk between GA and SL by disrupting the SMXL8-AGL9 interaction that represses HY5 transcription. Taken together, our study reveals the regulatory mechanism of SL-mediated anthocyanin biosynthesis and uncovers the role of SL-GA crosstalk in regulating anthocyanin biosynthesis in apple.

DNA vaccines targeting amyloid-ß oligomer ameliorate cognitive deficits of aged APP/PS1/tau triple-transgenic mouse models of Alzheimer's disease.

The amyloid-ß (Aß) oligomer, rather than the Aß monomer, is considered to be the primary initiator of Alzheimer's disease. It was hypothesized that p(Aß3-10)10-MT, the recombinant Aß3-10 gene vaccine of the Aß oligomer has the potential to treat Alzheimer's disease. In this study, we intramuscularly injected the p(Aß3-10)10-MT vaccine into the left hindlimb of APP/PS1/tau triple-transgenic mice, which are a model for Alzheimer's disease. Our results showed that the p(Aß3-10)10-MT vaccine effectively reduced Aß oligomer levels and plaque deposition in the cerebral cortex and hippocampus, decreased the levels tau protein variants, reduced synaptic loss, protected synaptic function, reduced neuron loss, and ameliorated memory impairment without causing any cerebral hemorrhaging. Therefore, this novel DNA vaccine, which is safe and highly effective in mouse models of Alzheimer's disease, holds a lot of promise for the treatment of Alzheimer's disease in humans.

Immunization with Aß3-10-KLH vaccine improves cognitive function and ameliorates mitochondrial dysfunction and reduces Alzheimer's disease-like pathology in Tg-APPswe/PSEN1dE9 mice.

Alzheimer's disease is a common cause of dementia, for which no disease-modifying therapy is yet available. Aß3-10-KLH, a vaccine for active immunization, has been shown to prevent pathological changes in young transgenic models of AD, but the effects of treatment with it and its effects on mitochondrial dysfunction remain unclear. We immunized 6-month-old Tg-APPswe/PSEN1dE9 mice with Aß3-10-KLH to analyze whether it is capable of eliminating amyloid-ß after its appearance. The vaccine effectively decreased amyloid-ß deposits, improved cognitive function and ameliorated mitochondrial dysfunction. These results indicate the potential of Aß3-10-KLH as a vaccine to treat AD.

Early active immunization with Aß3-10-KLH vaccine reduces tau phosphorylation in the hippocampus and protects cognition of mice.

Active and passive anti-Aß immunotherapies have successfully been used for the prevention and treatment of Alzheimer's disease animal models. However, clinical use of these immunotherapies is not effective, because the vaccination is administered too late. At 1 month of age, 100 µL of Aß3-10-KLH peptide (vaccine, 2 µg/µL) was subcutaneously injected into the neck of an amyloid precursor protein/presenilin-1/tau transgenic (3×Tg-AD) mouse model. Aß3-10-KLH peptide was re-injected at 1.5, 2.5, 3.5, 4.5, 5.5, and 6.5 months of age. Serum levels of Aß antibody were detected by enzyme-linked immunosorbent assay, while spatial learning and memory ability were evaluated by Morris water maze. Immunohistochemistry was used to detect total tau with HT7 and phosphorylated tau with AT8 (phosphorylation sites Ser202 and Thr205) and AT180 (phosphorylation site Thr231) antibodies in the hippocampus. In addition, western blot analysis was used to quantify AT8 and AT180 expression in the hippocampus. The results showed that after vaccine injection, mice produced high levels of Aß antibody, cognitive function was significantly improved, and total tau and phosphorylated tau levels were significantly reduced. These findings suggest that early active immunization with Aß3-10-KLH vaccine can greatly reduce tau phosphorylation, thereby mitigating the cognitive decline of 3×Tg-AD mice. This study was approved by the Animal Ethics Committee of China Medical University, China (approval No. 103-316) on April 2, 2016.

Reduction of amyloid beta by Aß3-10-KLH vaccine also decreases tau pathology in 3×Tg-AD mice.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive amyloid-ß (Aß) accumulation, neurofibrillary tangles (NFTs) formation and synaptic alterations. Active immunotherapy is regarded as one of the most promising strategies for AD prevention and treatment. In this research, we used APPswe/PS1M146 V/TauP301 L triple transgenic (3×Tg-AD) mice, in which the pathological changes are the most similar to those in AD patients. The Aß 3-10 -keyhole limpet haemocyanin (KLH) vaccine was administered to mice at 1 month, and no AD-associated changes were detected at that time. The vaccine effectively mitigated AD-like pathology and cognitive dysfunction in the 3×Tg-AD mice. Both soluble and insoluble Aß and tau protein in the brain tissues of the 3×Tg-AD mice were significantly decreased after the administration of Aß 3-10 -KLH. In addition, the level of phosphorylated tau also decreased following removal of the Aß pathological changes.

An Aß3-10-KLH vaccine reduced Alzheimer's disease-like pathology and had a sustained effect in Tg-APPswe/PSEN1dE9 mice.

Alzheimer's disease is a neurodegenerative disease that affects many patients worldwide. The amyloid cascade hypothesis has been adopted by most researchers as the mechanism underlying Alzheimer's disease. Aß plaques have been considered the core factor in the neurotoxic effect in Alzheimer's disease, though some controversy remains. Further effort is necessary to elucidate the mechanism and to develop effective treatments. Previous studies have indicated that eliminating Aß plaques could improve synaptic plasticity and cognitive function. Researchers have developed various forms of vaccines to prevent Aß deposition or eliminate Aß plaques and have made some progress. We developed a new vaccine, Aß3-10-KLH, to increase the level of the anti-Aß immune response, and we show that this vaccine resulted in a sustained prevention of Aß deposition at 4 months after cessation of the vaccine treatment. At the same time point, the expression of synaptophysin and NMDAR2B in APP/PS1 transgenic mice was increased by immunization.

Prophylactic active immunization with a novel epitope vaccine improves cognitive ability by decreasing amyloid plaques and neuroinflammation in APP/PS1 transgenic mice.

Both amyloid-ß peptide (Aß) deposition and neuroinflammation are considered to be early events that play pivotal roles in Alzheimer's disease (AD) pathogenesis and its associated cognitive impairment. Prophylactic anti-Aß active immunotherapy is a promising therapeutic strategy for AD, if the Aß-specific autoimmune responses to self T cell epitopes of Aß can be avoided. This can be achieved by the use of antigen, which contains the B cell epitope of Aß and excludes the Aß-specific T cell epitope. In this study, we developed a novel peptide epitope vaccine, Aß3-10-KLH, by coupling the B cell epitope Aß3-10 to keyhole limpet hemocyanin (KLH) as the carrier protein, and subcutaneously injected it into 2.5-month-old APP/PS1 transgenic mice. Aß3-10-KLH immunization induced high levels of anti-Aß antibodies and significantly improved cognitive ability in APP/PS1 transgenic mice. Immunohistochemistry and immunofluorescence revealed that Aß3-10-KLH immunization significantly reduced cerebral amyloid plaque formation and alleviated gliosis. The results indicate that Aß3-10-KLH immunization successfully rescued cognitive impairment in APP/PS1 transgenic mice via decreasing cerebral Aß deposition and neuroinflammation. Aß3-10-KLH may potentially be safe and effective for prevention and treatment of AD.

Active immunization with the peptide epitope vaccine Aß3-10-KLH induces a Th2-polarized anti-Aß antibody response and decreases amyloid plaques in APP/PS1 transgenic mice.

Active amyloid-ß (Aß) immunotherapy is effective in preventing Aß deposition, facilitating plaque clearance, and improving cognitive functions in mouse models of Alzheimer's disease (AD). Developing a safe and effective AD vaccine requires a delicate balance between inducing adequate humoral immune responses and avoiding T cell-mediated autoimmune responses. In this study, we designed 2 peptide epitope vaccines, Aß3-10-KLH and 5Aß3-10, prepared respectively by coupling Aß3-10 to the immunogenic carrier protein keyhole limpet hemocyanin (KLH) or by joining 5 Aß3-10 epitopes linearly in tandem. Young APP/PS1 mice were immunized subcutaneously with Aß3-10-KLH or 5Aß3-10 mixed with Freund's adjuvant, and the immunopotencies of these Aß3-10 peptide vaccines were tested. Aß3-10-KLH elicited a robust Th2-polarized anti-Aß antibody response and inhibited Aß deposition in APP/PS1 mice. However, 5Aß3-10 did not induce an effective humoral immune response. These results indicated that Aß3-10-KLH may be a safe and efficient vaccine for AD and that conjugating the antigen to a carrier protein may be more effective than linking multiple peptide antigens in tandem in applications for antibody production and vaccine preparation.

[Genome-wide identification and analyses of 4CL gene families in Pyrus bretschneideri Rehd].

4-coumaric acid: coenzyme A ligase (4CL) gene is one of the key genes involved in the regulation of lignin metabolism and the synthesis of flavonoid and other secondary metabolites in plant, while the synthesized and polymerized lignin is deposited in cell walls and leads to thickening of secondary walls in some parenchyma cells and formation of stone cells. To better understand the variety and quantity of 4CL genes in Pyrus bretschneideri Rehd., we used the amino acid and cDNA databases of Pyrus bretschneideri Rehd. genome to screen 4CL gene family, and analyzed their classification, evolutionary relationships, physical location, gene structure and conserved motif. Our results showed that 29 4CL genes were identified and preliminarily characterized, and these 4CL genes were distributed in all chromosomes except chromosomes 4, 8, 11, 12 and clustered on chromosomes 9 and 17 through gene location analysis. The relationship between 4CL gene structure and evolution was further determined by comparing gene structure and phylogenetic tree. These findings provide a basis for further analysis of 4CL gene function in Pyrus bretschneideri Rehd.

Nicorandil inhibits oxidative stress and amyloid-ß precursor protein processing in SH-SY5Y cells overexpressing APPsw.

It has been demonstrated that ATP-sensitive potassium (KATP) channel activation has neuroprotective effects against neuronal damage induced by hypoxia, ischemia or metabolism stress. This study investigated the multiply protective effects of KATP channel opener nicorandil against neurotoxicity in SH-SY5Y cells transiently transfected with Swedish mutant APP (APPsw) and also the potential involvement of PI3K/Akt/GSK-3ß pathway. Cells were treated with nicorandil (1 mM) for 24 h with and without glibenclamide (10 µM), a KATP channel inhibitor. Then the cells were collected for Hoechst33342, biochemical assays, real-time PCR, western blot and ELISA assay. Our results showed that nicorandil reduced apoptosis and decreased oxidative stress. Moreover, nicorandil down regulated APP695 mRNA and APP695 protein expression, also reduced Aß1-42 levels in the medium. In addition, nicorandil increased the protein levels of p-Akt and p-GSK-3ß by PI3K activation. Applying a PI3K inhibitor, LY294002 blocked the protection. These findings suggest nicorandil to be a potential therapeutic agent to treat Alzheimer's disease (AD).

Active Immunization with DNA Vaccine Reduced Cerebral Inflammation and Improved Cognitive Ability in APP/PS1 Transgenic Mice by In Vivo Electroporation.

The aggregation of amyloid ß-peptide (Aß) is thought to play a pivotal role in the disease progression of Alzheimer's disease (AD). Amyloid ß directed immunotherapy has been considered an alternative AD treatment. In this study, we constructed a DNA vaccine, p(Aß3-10)10-mIL-4, encoding ten tandem repeats of Aß3-10 fused with mouse IL-4. Eight-month-old APP/PS1 transgenic mice were injected intramuscularly with p(Aß3-10)10-mIL-4 followed by in vivo electroporation. Immunization with the vaccine induced high-titer anti-Aß antibodies and attenuated the behavior impairment. Immunoglobulin isotyping revealed a predominantly IgG1 response and ex vivo cultured splenocytes exhibited a low IFN-γ and high IL-4 response, indicating a Th2 anti-inflammatory response. Immunohistochemical analysis revealed that p(Aß3-10)10-mIL-4 immunization decreased Aß deposition, and the microglial attraction significantly decreased accompanied by the clearance of Aß. There was no microhemorrhage in the brain of the immunized mice. These results suggest that the immunization potentially reduced the inflammation in brain of transgenic mice and therefore improved their cognitive ability. This novel DNA vaccine p(Aß3-10)10-mIL-4 may be an effective immunization method as therapy for AD.

Common Polymorphisms in the GSK3ß Gene May Contribute to the Pathogenesis of Alzheimer Disease: A Meta-Analysis.

OBJECTIVE: Although it is well known that GSK3ß participates in the proliferation and survival of various tumor cells, its role in diseases of the central nervous system has been sparsely documented. In the past few years, studies regarding the relationship between GSK3ß rs334558 T>C and rs6438552 C>T polymorphisms and Alzheimer disease (AD) risk have yielded contradictory results. As such, this meta-analysis seeks to satisfy the need to further investigate this relationship. METHODS: In this research, published studies regarding the association of GSK3ß rs6438552 and rs334558 mutation with AD risk was systematically assessed. Studies were retrieved from MEDLINE, Science Citation Index, the Cochrane Library, PubMed, Embase, CINAHL, Current Contents Index, Chinese Biomedical, Chinese Journal Full-Text, and Weipu Journal. Pooled odds ratios and 95% confidence intervals were calculated for allele contrast and homozygous, heterozygous, dominant, and recessive genetic model comparisons. RESULTS: It was found that GSK3ß rs334558 T>C and rs6438552 C>T polymorphisms were correlated with susceptibility to AD under 4 genetic models (all P<.05). In country-stratified subgroups, the results showed increased risk of developing AD in rs334558 T>C polymorphism among Chinese and Spain populations in majority groups. GSK3ß rs6438552 C>T polymorphism was correlated with increased the risk of developing AD only in Australian populations. CONCLUSION: Our findings suggest that there exists a significant association between GSK3ß rs334558 T>C polymorphism and increased susceptibility of AD. Moreover, future updated studies with stratified case-control population are warranted for validation studies.

Alterations in cholesterol and ganglioside GM1 content of lipid rafts in platelets from patients with Alzheimer disease.

The aim of this study was to investigate the changes in the protein, cholesterol, and ganglioside GM1 content of lipid rafts in platelets from patients with Alzheimer disease (AD), and identify potential blood biomarkers of the disease. A total of 31 Chinese patients with AD and 31 aged-matched control subjects were selected. Lipid rafts were isolated from platelets using Optiprep gradient centrifugation. The protein content of lipid rafts was evaluated using Micro BCA assay, the cholesterol content using molecular probes, ganglioside GM1 content using colorimetry and dot-blotting analysis. The results showed that the cholesterol and ganglioside GM1 content of lipid rafts from platelets was significantly higher in patients with AD than aged-matched control subjects, whereas the protein content of lipid rafts did not show any differences between the 2 groups. These results indicate that the increases in the cholesterol and ganglioside GM1 content of lipid rafts from the platelets of patients with AD might serve as a biochemical adjunct to the clinical diagnosis of AD.

Esophageal sarcomatoid carcinoma presenting as a Fever with elevated serum leukocytes.

The study presented a case of esophageal cancer presenting as intermittent fever with markedly elevated serum leukocyte and C-reactive protein. The patient's symptoms had not improved with antibiotic treatment. However, after thoracic esophagectomy, the fever faded and leukocyte serum levels rapidly normalized.

Active immunotherapy facilitates Aß plaque removal following through microglial activation without obvious T cells infiltrating the CNS.

Immunization of AD mouse models with Aß reduced Aß deposits and improved memory and learning deficits, but some clinical trials of immunization with Aß were halted due to brain inflammation which was presumably induced by a T cell-mediated autoimmune response. We have developed a "possibly safer" vaccine. Our results demonstrate that pcDNA3.1 vector encoding ten repeats of Aß3-10 fragments elicited high titers of antibodies which reacted well with not only monomeric but also oligomeric and fibrillar forms of Aß42 peptide. Induced antibodies strongly reacted with amyloid plaques in the brain, demonstrating functional activity of the antibodies. Immunohistochemical and immunofluorescence showed there was significantly less plaque deposition accomplied with less microglia activation as detected both in the frontal cortex and hippocampus. These data suggested that microglial activation is necessary for efficient removal of compact amyloid deposits with immunotherapy. No obvious inflammation T cell and Prussian blue positive cell was found indicated that inflammation T cell infiltration and microhemmorage can be avoided or at least reduced to the minimum level.

Tyrosine phosphatase STEP61 negatively regulates amyloid ß-mediated ERK/CREB signaling pathways via α7 nicotinic acetylcholine receptors.

Striatal-enriched phosphatase 61 (STEP61 ) plays an essential role in synaptic plasticity and has recently been implicated in neurodegenerative disease. Here we characterized a possible role of STEP61 in Alzheimer's disease (AD) pathology using a mouse model of AD (Tg-APPswe/PSEN1dE9, APP/PS1 mice) and an in vitro model of AD [cortical neurons treated with amyloid ß (Aß)1-42 peptides]. Our data indicate age-related elevation of STEP61 levels and the proportion of dephosphorylated STEP61 (active STEP61 ) in wild-type mice, which was enhanced in APP/PS1 mice. Furthermore, the increased STEP61 levels and active STEP61 were observed in the hippocampus and cortex from 12-month-old APP/PS1 mice and in Aß1-42 -treated cortical neurons. An α7 nicotinic acetylcholine receptors (nAChRs) antagonist, α-bungarotoxin (BTX), inhibited the Aß1-42 -induced increase of STEP61 expression and activation. In addition, extracellular signal-regulated kinase 1/2 (ERK1/2) and cAMP response element binding (CREB) were impaired in Aß1-42 -treated cortical neurons, and knockdown of STEP61 enhanced the activation of ERK1/2 and CREB. Collectively, these findings indicate two alternate pathological pathways effecting STEP61 regulation in AD. First, Aß regulating STEP61 activity is mediated by Aß binding to α7 nAChRs. Second, STEP61 negatively regulates Aß-mediated ERK/CREB pathway, an important signaling cascade involved in memory formation.

CXCL1 contributes to ß-amyloid-induced transendothelial migration of monocytes in Alzheimer's disease.

BACKGROUND: Bone marrow-derived microglia that originates in part from hematopoietic cells, and more particularly from monocytes preferentially attach to amyloid deposition in brains of Alzheimer's disease (AD). However, the mechanism of monocytes recruited into the amyloid plaques with an accelerated process in AD is unclear. METHODOLOGY/PRINCIPAL FINDINGS: Here we reported that monocytes from AD patients express significantly higher chemokine (C-X-C motif) ligand 1 (CXCL1) compared to age-matched controls. AD patient's monocytes or CXCL1-overexpressing THP-1 cells had enhanced ability of ß-amyloid (Aß)-induced transendothelial migration and Aß-induced transendothelial migration for AD patient's monocytes or CXCL1-overexpressing THP-1 cells was almost abrogated by anti-CXCL1 antibody. Furthermore, monocytes derived from a transgenic mouse model of AD also expressed significantly higher CXCL1. CD11b⁺CD45(hi) population of cells that were recruited from the peripheral blood were markedly bolcked in APP mouse brain by anti-CXCL1 antibody. Accordingly, in response to Aß, human brain microvascular endothelial cells (HBMEC) significantly up-regulated CXC chemokine receptor 2 (CXCR2) expression, which was the only identified receptor for CXCL1. In addition, a high level expression of CXCR2 in HBMEC significantly promoted the CXCL1-overexpressing THP-1 cells transendothelial migration, which could be was abrogated by anti-CXCR2 antibody. Further examination of possible mechanisms found that CXCL1-overexpressing THP-1 cells induced transendothelial electrical resistance decrease, horseradish peroxidase flux increase, ZO-1 discontinuous and occludin re-distribution from insoluble to soluble fraction through interacting with CXCR2. ROCK inhibitor, Y27632, could block CXCL1-overexpressing THP-1 cells transendothelial migration, whereas other inhibitors had no effects. CONCLUSIONS/SIGNIFICANCE: The present data indicate that monocytes derived from AD patients overexpressing CXCL1, which is a determinant for Aß-induced transendothelial migration. CXCL1 expressed by monocytes and CXCR2 on HBMEC is involved in monocytes migrating from blood to brain in AD patients.

(-)-Epigallocatechin-3-gallate alleviates spatial memory impairment in APP/PS1 mice by restoring IRS-1 signaling defects in the hippocampus.

Alzheimer's disease (AD) fundamentally represents a metabolic disease associated with brain insulin resistance. TNF-α/c-Jun N-terminal kinase (JNK) signaling plays a central role in serine phosphorylation of insulin receptor substrate-1 (IRS-1). (-)-Epigallocatechin-3-gallate (EGCG), a potent antioxidant, has been verified to attenuate peripheral insulin resistance by reducing IRS-1 signaling blockage. This study aimed to investigate the effects and possible mechanisms of EGCG on central IRS-1 signaling in vivo. APP/PS1 mice were treated with EGCG, and spatial memory was assessed by the Morris water maze test. Levels of soluble and insoluble Aß42 in the hippocampus were determined by ELISA. The activation of NF-α/JNK and IRS signaling was detected by immunohistochemistry and Western blot analysis. Our results showed that EGCG ameliorated the impaired learning and memory in APP/PS1 mice. Notably, we found a significant reduction of IRS-1pS636 level accompanied with decreased Aß42 levels in the hippocampus of 13-month-old female APP/PS1 mice after treatment with EGCG (2 or 6 mg/kg/day) for 4 weeks. Furthermore, EGCG treatment inhibited TNF-α/JNK signaling and increased the phosphorylation of Akt and glycogen synthase kinase-3ß in the hippocampus of APP/PS1 mice. In conclusion, our study provides evidence that long-term consumption of EGCG may alleviate AD-related cognitive deficits by effectively attenuating central insulin resistance.

Intranasal inoculation with an adenovirus vaccine encoding ten repeats of Aß3-10 reduces AD-like pathology and cognitive impairment in Tg-APPswe/PSEN1dE9 mice.

To develop a safe and efficient vaccine for AD treatment, we constructed an adenovirus vector vaccine encoding ten repeats of Aß3-10 and CpG motif as a molecular adjuvant. We demonstrated that therapeutic immunization with Ad-10×Aß3-10-CpG elicits Aß3-10 specific Th2-polarized immune response with high titers of anti-Aß antibodies in APPswe/PSEN1dE9 mice, which in turn reduced Aß deposits in brains and cognitive impairment. In addition, Ad-10×Aß3-10-CpG reduced astrocytosis without increasing the incidence of microhemorrhage. Our findings of this study raise the possibility that the adenovirus vaccine Ad-10×Aß3-10-CpG would be a safe and effective alternative for AD immunotherapy.

In vivo electroporation of a new gene vaccine encoding ten repeats of Aß3-10 prevents brain Aß deposition and delays cognitive impairment in young Tg-APPswe/PSEN1dE9 mice.

Active immunization holds great promise for the treatment of Alzheimer's disease but the infiltration of T-lymphocytes and associated meningoencephalitis observed in clinical trials needs to be overcome. To avoid this toxicity, previous studies have used synthetic truncated derivatives of Aß to promote humoral immunity. In this study, we developed a novel vaccine [p(Aß3-10)10-MT] that expresses ten repeats of Aß3-10 with melatonin (MT) as an adjuvant, and administered it intramuscularly in three-month-old Tg-APPswe/PSEN1dE9 (Tg) mice by in vivo electroporation. The p(Aß3-10)10-MT vaccine induced high titers of anti-Aß antibodies, which in turn reduced Aß deposits in the mouse brains and decreased cognitive impairment. Immunoglobulin isotyping revealed a predominantly IgG1 response, indicating a Th2 anti-inflammatory response. Ex vivo cultured splenocytes exhibited a low IFN-γ and high IL-4 response. Immunohistochemical analysis revealed that glial cell activation was also attenuated. These results indicate that p(Aß3-10)10-MT may potentially be an effective vaccine to reduce accumulated Aß and attenuate cognitive deficits.