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Oliver Goldhardt

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YNICL Journal 2025 Journal Article

Partial volume effect correction impairs the diagnostic utility of [18F]-THK-5351 PET in nonfluent-agrammatic variant primary progressive aphasia

  • Patrick J. Sommer
  • Sebastian Schuster
  • Oliver Goldhardt
  • Nobuyuki Okamura
  • Felix Mueller-Sarnowski
  • Maximilian Scheifele
  • Florian Eckenweber
  • Annika Kreuzer

OBJECTIVES: F]-THK-5351 PET a marker of reactive neuroinflammatory astrogliosis as well as tau-binding. METHODS: F]-THK-5351 PET signal differences between nfv-PPA and controls before and after PVEC. Additionally, a blinded visual read was performed by three nuclear medicine physicians (consensus) before and after PVEC. RESULTS: F]-THK-5351 tracer uptake was significantly higher in the bilateral frontal cortex of patients with nfv-PPA when compared to HC (left > right), despite significant grey matter atrophy in the same brain regions in patients with nfv-PPA. SUVr differences between nfv-PPA and HC were further increased by PVEC in frontal brain regions, but group level variance increased in parallel and reduced the number of significant differences between SUVr of nfv-PPA and HC (uncorrected: 10 significant regions, CoV[nfv-PPA]: 20.8 % ± 4.7 %, CoV[HC]: 7.9 % ± 2.4 %/PVEC: 3 significant regions, CoV[nfv-PPA]: 28.4 % ± 8.9 %, CoV[HC]: 9.8 % ± 2.5 %). Sensitivity/specificity of the visual read for detection of nfv-PPA was 0.85/1.00 without PVEC and 0.85/0.75 with PVEC. CONCLUSIONS: F]-THK-5351 images in patients with nfv-PPA is impaired by PVEC due to loss of specificity and does not support the use of PVEC even in patients with severe atrophy.

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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.

Details DOI
v2026.09.13