IgM response against amyloid-beta in aging: a potential peripheral protective mechanism.
IgM response against amyloid-beta in aging: a potential peripheral protective mechanism.
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DOI：
10.1186/s13195-018-0412-9
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发表时间：
2018-08-16
期刊：
影响因子：
--
通讯作者：
Agrawal A
中科院分区：
文献类型：
--
作者：
Agrawal S;Abud EM;Snigdha S;Agrawal A
The immune system plays a major role in the pathogenesis of age-related dementia, including Alzheimer’s disease (AD). An insight into age-associated changes in the immune response to amyloid-beta (Aβ) in individuals without AD may be beneficial in identifying mechanisms preventing accumulation of Aβ. We examined the response of human monocyte-derived dendritic cells (DCs), T cells, and peripheral blood mononuclear cells (PBMCs) from healthy aged and young subjects to Aβ peptide 1–42, Aβ fibrils, and recombinant, nonaggregated tau-4 protein with a view to understand the role of peripheral immunity in AD. Our studies revealed that DCs from healthy aged subjects display weak reactivity towards the Aβ peptide and no reactivity towards Aβ fibrils and tau compared with their young counterparts. An analysis of old and young PBMCs revealed that there is no significant T-cell memory against Aβ peptide, fibrils, or tau. Remarkably, the plasma levels of IgM antibodies specific to Aβ peptide 1–42 were significantly increased in aged subjects compared with young subjects, while IgG levels were comparable. Aβ peptide-specific IgM and IgG levels were also determined in the plasma of AD subjects compared with age-matched controls to demonstrate that the immune response against Aβ is stronger in AD patients. A decline in Aβ peptide-specific IgM antibodies was observed in AD patients compared with age-matched controls. In contrast, the levels of IgG as well as interleukin-21, the major cytokine involved in class switching, were increased in AD and patients with mild cognitive impairment, indicating a strong immune response against Aβ. Collectively, low immunogenicity of Aβ in healthy controls may prevent inflammation while the generation of specific IgM antibodies may help in the clearance of Aβ in healthy subjects. The online version of this article (10.1186/s13195-018-0412-9) contains supplementary material, which is available to authorized users.
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DOI：
10.1084/jem.20031763
发表时间：
2004-12-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chang MK;Binder CJ;Miller YI;Subbanagounder G;Silverman GJ;Berliner JA;Witztum JL
通讯作者：
Witztum JL
影响因子：
15.1
作者：
Ciaramella, Antonio;Salani, Francesca;Bossu, Paola
通讯作者：
Bossu, Paola
影响因子：
16.2
作者：
Abud EM;Ramirez RN;Martinez ES;Healy LM;Nguyen CHH;Newman SA;Yeromin AV;Scarfone VM;Marsh SE;Fimbres C;Caraway CA;Fote GM;Madany AM;Agrawal A;Kayed R;Gylys KH;Cahalan MD;Cummings BJ;Antel JP;Mortazavi A;Carson MJ;Poon WW;Blurton-Jones M
通讯作者：
Blurton-Jones M
影响因子：
15.9
作者：
Binder, CJ;Hartvigsen, K;Witztum, JL
通讯作者：
Witztum, JL
DOI：
10.1002/ajmg.b.30456
发表时间：
2007-06-05
影响因子：
2.8
作者：
Harold, D.;Jehu, L.;Williams, J.
通讯作者：
Williams, J.