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Panagiotis Alexopoulos

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YNICL Journal 2014 Journal Article

LRP-1 polymorphism is associated with global and regional amyloid load in Alzheimer's disease in humans in-vivo

  • Timo Grimmer
  • Oliver Goldhardt
  • Liang-Hao Guo
  • Behrooz H. Yousefi
  • Stefan Förster
  • Alexander Drzezga
  • Christian Sorg
  • Panagiotis Alexopoulos

OBJECTIVE: Impaired 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 [(11)C]PiB. MATERIALS AND METHODS: 72 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. RESULTS: The 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. DISCUSSION: In 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.

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YNIMG Journal 2008 Journal Article

Multivariate and univariate neuroimaging biomarkers of Alzheimer's disease

  • Christian Habeck
  • Norman L. Foster
  • Robert Perneczky
  • Alexander Kurz
  • Panagiotis Alexopoulos
  • Robert A. Koeppe
  • Alexander Drzezga
  • Yaakov Stern

We performed univariate and multivariate discriminant analysis of FDG–PET scans to evaluate their ability to identify Alzheimer's disease (AD). FDG–PET scans came from two sources: 17 AD patients and 33 healthy elderly controls were scanned at the University of Michigan; 102 early AD patients and 20 healthy elderly controls were scanned at the Technical University of Munich, Germany. We selected a derivation sample of 20 AD patients and 20 healthy controls matched on age with the remainder divided into 5 replication samples. The sensitivity and specificity of diagnostic AD-markers and threshold criteria from the derivation sample were determined in the replication samples. Although both univariate and multivariate analyses produced markers with high classification accuracy in the derivation sample, the multivariate marker's diagnostic performance in the replication samples was superior. Further, supplementary analysis showed its performance to be unaffected by the loss of key regions. Multivariate measures of AD utilize the covariance structure of imaging data and provide complementary, clinically relevant information that may be superior to univariate measures.

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v2026.09.13