کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3075322 | 1580963 | 2014 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: LRP-1 polymorphism is associated with global and regional amyloid load in Alzheimer's disease in humans in-vivo LRP-1 polymorphism is associated with global and regional amyloid load in Alzheimer's disease in humans in-vivo](/preview/png/3075322.png)
• Impaired drainage systems are discussed to be causative for AD.
• LRP-1 transports Aß from the brain.
• LRP-1 polymorphism is associated with amyloid deposition in-vivo in-human.
• Results are compatible with the hypothesis of impaired drainage systems in AD.
ObjectiveImpaired amyloid clearance has been proposed to contribute to β-amyloid deposition in sporadic late-onset Alzheimer's disease (AD). Low density lipoprotein receptor-related protein 1 (LRP-1) is involved in the active outward transport of β-amyloid across the blood–brain barrier (BBB). The C667T polymorphism (rs1799986) of the LRP-1 gene has been inconsistently associated with AD in genetic studies.We aimed to elucidate the association of this polymorphism with in-vivo brain amyloid load of AD patients using amyloid PET with [11C]PiB.Materials and methods72 patients with very mild to moderate AD were examined with amyloid PET and C667T polymorphism was obtained using TaqMan PCR assays. The association of C667T polymorphism with global and regional amyloid load was calculated using linear regression and voxel based analysis, respectively. The effect of the previously identified modulator of amyloid uptake, the apolipoprotein E genotype, on this association was also determined.ResultsThe regression analysis between amyloid load and C667T polymorphism was statistically significant (p = 0.046, β = 0.236). In an additional analysis ApoE genotype and gender were identified to explain further variability of amyloid load. Voxel based analysis revealed a significant (p < 0.05) association between C667T polymorphism and amyloid uptake in the temporo-parietal cortex bilaterally. ApoE did not interact significantly with the LRP-1 polymorphism.DiscussionIn conclusion, C667T polymorphism of LRP-1 is moderately but significantly associated with global and regional amyloid deposition in AD. The relationship appears to be independent of the ApoE genotype. This finding is compatible with the hypothesis that impaired amyloid clearance contributes to amyloid deposition in late-onset sporadic AD.
Journal: NeuroImage: Clinical - Volume 4, 2014, Pages 411–416