Association of the CX3CR1-V249I Variant with Neurofibrillary Pathology Progression in Late-Onset Alzheimer's Disease
| Autor: | Jose M. Vidal-Taboada, Diana Maria Lopategui, Ellen Gelpi, Alan Lopez-Lopez |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Pathology medicine.medical_specialty Neurology Neuroscience (miscellaneous) CX3C Chemokine Receptor 1 Late onset Disease Biology Pathogenesis Cohort Studies 03 medical and health sciences Cellular and Molecular Neuroscience Cerebellar Cortex Random Allocation 0302 clinical medicine Alzheimer Disease medicine Humans Neuroinflammation Genetic Association Studies Aged Retrospective Studies Aged 80 and over Case-control study Genetic Variation Neurofibrillary Tangles Middle Aged medicine.disease 030104 developmental biology Cerebellar cortex Case-Control Studies Disease Progression Female Alzheimer's disease 030217 neurology & neurosurgery |
| Zdroj: | Molecular neurobiology. 55(3) |
| ISSN: | 1559-1182 |
| Popis: | Neuroinflammation and microglial dysfunction have a prominent role in the pathogenesis of late-onset Alzheimer's disease (LOAD). CX3CR1 is a microglia-specific gene involved in microglia-neuron crosstalk and neuroinflammation. Numerous evidence show the involvement of CX3CR1 in AD. The aim of this study was to investigate if some functional genetic variants of this gene could influence on LOAD's outcome, in a neuropathologically confirmed Spanish cohort. We designed an open, pragmatic, case-control retrospective study including a total of 475 subjects (205 pathologically confirmed AD cases and 270 controls). We analyzed the association of the two CX3CR1 functional variants (V249I, rs3732379; and T280M, rs3732378) with neurofibrillary pathology progression rate according to Braak's staging system, age at onset (AAO), survival time, and risk of suffering LOAD. We found that individuals heterozygous for CX3CR1-V249I presented a lower neurofibrillary pathology stage at death (OR = 0.42, 95%CI [0.23, 0.74], p = 0.003, adj-p = 0.013) than the other genotypes. Eighty percent of the subjects homozygous for 249I had higher neurofibrillary pathology progression (Braak's stage VI). Moreover, homozygosis for 280M and 249I could be associated with a higher AAO in the subgroups of AD with Lewy bodies and without Lewy bodies. These CX3CR1 genetic variants could represent new modifying factors of pathology progression and age at onset in LOAD. These results provide further evidence of the involvement of CX3CR1 pathway and microglia/macrophages in the pathogenesis of LOAD. |
| Databáze: | OpenAIRE |
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