Complement receptor 1 polymorphisms and risk of late-onset Alzheimer's disease

Zhang, Qun; Yu, Jin‐Tai; Zhu, Qi-Xiu; Zhang, Wei; Wu, Zhong-Chen; Miao, Dengshun; Tan, Lan

doi:10.1016/j.brainres.2010.06.018

Cited by 46 publications

(25 citation statements)

References 40 publications

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“…A second independent AD GWAS performed using the European Alzheimer's Disease Initiative sample (EADI) showed genome-wide significant evidence for association with CLU (P=7.5x10 -9 ) and CR1 (P=3.7x10 -9 ), and support for PICALM (P=3x10 -3 ). The associations in CLU, PICALM and CR1 have been replicated in several independent datasets [3][4][5][6] and shown relationships with neurodegenerative processes underlying disease 7 . In addition, Seshadri and colleagues reported genome-wide significant association for BIN1 (P=1.6x10 -11 ) when combining GERAD1 and EADI data with data from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) 8 .…”

Section: Introductionmentioning

confidence: 78%

P1‐236: Genome‐Wide Association Study for Alzheimer's Disease with Psychotic Symptoms

Hollingworth

Sweet

Sims

et al. 2011

Alzheimer's & Dementia

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Section: Introductionmentioning

confidence: 78%

P1‐236: Genome‐Wide Association Study for Alzheimer's Disease with Psychotic Symptoms

Hollingworth

Sweet

Sims

et al. 2011

Alzheimer's & Dementia

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“…Carbohydrates and their receptors play an important role in the polarization of microglia and its potential repair function. Therefore, novel carbohydrates based drugs and gene delivery systems have been suggested as new therapeutic strategies (Zhang et al 2010b). In this context, siglecs are thought to be suitable target molecules.…”

Section: Discussionmentioning

confidence: 99%

Microglial carbohydrate-binding receptors for neural repair

2012

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Microglia are the resident immune cells of the central nervous system (CNS) and perform typical scavenging and innate immune functions. Their capacity to eliminate extracellular aggregates and apoptotic neural material without inflammation is crucial for brain tissue homeostasis and repair. To fulfill these tasks, microglia express a whole set of recognition receptors including toll-like (TLRs), carbohydrate-binding, Fc, complement and cytokine receptors. Receptors recognizing carbohydrate structures are strongly involved in microglial repair function. Carbohydrate-binding receptors can be divided into two major subgroups: the sulfated glycosaminoglycan (SGAG)-binding receptors and the lectins (Siglecs, galectins, selectins). SGAG-binding receptors recognize anionic structural motifs within extended SGAG chains. Siglecs bind to the sialic acid cap of the intact glycocalyx. Other lectin family members such as galectins recognize lactosamine units typically exposed after alteration of the glycocalyx. Dependent on the type of microglial carbohydrate-binding receptors that are stimulated, either a pro-inflammatory cytotoxic or an anti-inflammatory repair-promoting response is evoked. The carbohydrate-binding receptors are also crucial in regulating microglial function such as phagocytosis during neurodegenerative or neuroinflammatory processes. A balance between microglial carbohydrate-binding receptor signaling via an immunoreceptor tyrosine-based activation motif or an immunoreceptor tyrosine-based inhibitory motif is required to polarize microglial cells appropriately so that they create a microenvironment permissive for neural regenerative events.

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“…In populations with contrasting origins, CR1 and CLU were associated with the AD risk in Chinese people [24,25] but not in African Americans, Caribbean Hispanics or subjects of a genetically isolated Arab community in Israel [22]. However, the studied ethnic case-control studies were clearly underpowered.…”

Section: Introductionmentioning

confidence: 90%