Immunotherapeutic efficiency of a tetravalent Aβ1-15 vaccine in APP/PS1 transgenic mice as mouse model for Alzheimer’s disease

Guan, Xiaoying; Yang, Jiliang; Gu, Huaiyu; Zou, Juntao; Ye, Zhibin

doi:10.4161/hv.24830

Cited by 20 publications

(12 citation statements)

References 33 publications

(31 reference statements)

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“…4,12 We previously found that the antigen 4Ab1-15 markedly inhibited inflammatory factors activated excessively in APP/PS1 transgenic mice, which is associated with the phagocytosis of microglial to clear the Ab plaques. 9 Meanwhile, clinical Alzheimer's diagnosis can be classified and predicted based on some biological indicators, 6,13 and the anti-inflammation antigen can be used to treat AD. Considering the convenience of inflammatory factors detection in sera, we conducted this study to research the relationship between the changing processes of the inflammatory response and the pathologic alterations.…”

Section: Discussionmentioning

confidence: 99%

“…The calibration curve for the determination of the anti-A b antibody concentration was based on the monoclonal antibody 6E10 diluted in different known concentrations and used as a positive control. 9,10 Absorbance was measured at 450 nm with a spectrophotometer. Anti-A b antibody titers were calculated using the statistics software Curve Expert 1.3.…”

Section: Samples and Immunization Protocolmentioning

confidence: 99%

“…The ratio of IFN-g to IL-4 in the brain, representing the balance of Th1/Th2, [8][9][10] was calculated and standardized to controls. The bias presented a similar fluctuation that showed Th1-polarized and then Th2-polarized immune response (Fig.…”

Section: Ab1-15 Increases Anti-ab Antibody Concentrations In Sera Anmentioning

confidence: 99%

“…The 4A b1-15 was emulsified 1:1 with MF59 adjuvant to 1 mg/ml. 4,9 Each mouse was treated with 0.1 ml subcutaneously. Indexes in sera were detected after each vaccination during a total 6 immunizations.…”

Section: Samples and Immunization Protocolmentioning

confidence: 99%

“…The dorsal hippocampus and the cerebral cortex were chosen for quantitative analysis. 9 Sections of each anatomic region of interest (hippocampus and cortex) were quantified using Image-Pro Plus 6.0 image analysis software, which was capable of color segmentation and automation via programmable macros. 19 The A b immunoreaction stained areas were expressed as a percentage of the total brain region tissue area, as was the quantitative image analysis of the microglial cell immunoreactivity.…”

Section: Quantitative Image Analysismentioning

confidence: 99%

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Continuous vaccinations of 4Aβ1-15 induces specific fluctuation of inflammatory factors accompany with pathologic alterations alleviation in APP/PS1 mice

Zhang¹,

Zou³

et al. 2015

Human Vaccines & Immunotherapeutics

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#These authors equally contributed to this work.Keywords: Ab burdens, APP/PS1 mice, continuous vaccinations, immunotherapy, inflammatory factors, microglial activation spatial learning and memory ability, specific fluctuationsAbbreviations: 4Ab1-15, 4 alternative tandem repeats of GPGPG-linked Ab1-15 sequences; Ab, b-amyloid; APP, amyloid precursor protein; IFN-g, interferon-g; IgG, immunoglobulin G; IL-1b, interleukin-1b; IL-4, interleukin-4; PS1, presenilin-1; Th, T-helper type; TNF-a, tumor necrosis factor-aThe common pathological hallmark of Alzheimer's disease (AD) is b-amyloid plaques deposition. Immunotherapy is a revolutionary pharmacological treatment for AD, aiming at improving plaque clearance while concomitantly decreasing inflammation. Our previous study prepared antigen 4Ab1-15 and found that it could alleviate pathologic alterations in APP/PS1 transgenic mice. The objective of our study was to research the changing processes induced by immunotherapy, including the inflammatory factor levels and microglial activation that is closely associated with Ab burdens clearance. APP/PS1 mice were injected with 4Ab1-15 6 times. Each time, the inflammatory factors in sera were detected, and a specific fluctuation that first increased and then decreased was found, in which there was a turning point after the third injection. It prompted us to further detect the indicators in the brains after the third injection and the sixth injection. The results showed that the therapeutic effects for Ab burdens and behaviors were continuously improved during the whole immune processes, whereas the inflammatory factor levels and microglial activation experienced similar specific fluctuations. The novel discovery may provide convenient methods for further detection and evaluation of immunotherapy in disease courses.

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Section: Discussionmentioning

confidence: 99%

Section: Samples and Immunization Protocolmentioning

confidence: 99%

Section: Ab1-15 Increases Anti-ab Antibody Concentrations In Sera Anmentioning

confidence: 99%

Section: Samples and Immunization Protocolmentioning

confidence: 99%

Section: Quantitative Image Analysismentioning

confidence: 99%

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Continuous vaccinations of 4Aβ1-15 induces specific fluctuation of inflammatory factors accompany with pathologic alterations alleviation in APP/PS1 mice

Zhang¹,

Zou³

et al. 2015

Human Vaccines & Immunotherapeutics

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Pharmacogenomics of Alzheimer’s Disease: Novel Therapeutic Strategies for Drug Development

Cacabelos

Torrellas

et al. 2014

Methods in Molecular Biology

165

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Alzheimer's disease (AD) is a major problem of health and disability, with a relevant economic impact on our society. Despite important advances in pathogenesis, diagnosis, and treatment, its primary causes still remain elusive, accurate biomarkers are not well characterized, and the available pharmacological treatments are not cost-effective. As a complex disorder, AD is a polygenic and multifactorial clinical entity in which hundreds of defective genes distributed across the human genome may contribute to its pathogenesis. Diverse environmental factors, cerebrovascular dysfunction, and epigenetic phenomena, together with structural and functional genomic dysfunctions, lead to amyloid deposition, neurofibrillary tangle formation, and premature neuronal death, the major neuropathological hallmarks of AD. Future perspectives for the global management of AD predict that genomics and proteomics may help in the search for reliable biomarkers. In practical terms, the therapeutic response to conventional drugs (cholinesterase inhibitors, multifactorial strategies) is genotype-specific. Genomic factors potentially involved in AD pharmacogenomics include at least five categories of gene clusters: (1) genes associated with disease pathogenesis; (2) genes associated with the mechanism of action of drugs; (3) genes associated with drug metabolism (phase I and II reactions); (4) genes associated with drug transporters; and (5) pleiotropic genes involved in multifaceted cascades and metabolic reactions. The implementation of pharmacogenomic strategies will contribute to optimize drug development and therapeutics in AD and related disorders.

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New progress in active immunotherapy targeting to amyloid beta

Gao

Chen

2015

Sci. China Chem.

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Immunotherapeutic efficiency of a tetravalent Aβ1-15 vaccine in APP/PS1 transgenic mice as mouse model for Alzheimer’s disease

Cited by 20 publications

References 33 publications

Continuous vaccinations of 4Aβ1-15 induces specific fluctuation of inflammatory factors accompany with pathologic alterations alleviation in APP/PS1 mice

Continuous vaccinations of 4Aβ1-15 induces specific fluctuation of inflammatory factors accompany with pathologic alterations alleviation in APP/PS1 mice

Pharmacogenomics of Alzheimer’s Disease: Novel Therapeutic Strategies for Drug Development

New progress in active immunotherapy targeting to amyloid beta

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