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Peer-reviewedCC BY 4.0European Journal of Nuclear Medicine and Molecular Imaging

Effect of genetic factors on [18F]FDG PET metabolic phenotypes in dementia with Lewy bodies

  • Sofie Lövdal1,2
  • Sanne K. Meles3
  • Giulia Carli4,5
  • Anna Dortmond3
  • Rosalie V. Kogan1
  • Orly Goldstein6
  • Mali Gana-Weisz6
  • Rotem I. Orad7
  • Roy N. Alcalay7,8,9
  • Noa Bregman7,10,9
  • Klaus L. Leenders1
  • Tamara Shiner7,8,10,9
10 affiliations
  1. 1Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
  2. 2Bernoulli Institute for Mathematics, Computer Science and Artificial Intelligence, University of Groningen, Groningen, the Netherlands
  3. 3Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
  4. 4Morris K. Udall Center of Excellence for Parkinson’s Disease Research, University of Michigan, Ann Arbor, MI USA
  5. 5Department of Radiology, University of Michigan, Ann Arbor, MI USA
  6. 6Laboratory of Biomarkers and Genomics of Neurodegeneration. Tel-Aviv Medical Center, Tel-Aviv, Israel
  7. 7Gray Faculty of Medical & Health Sciences, Tel-Aviv University, Tel-Aviv, Israel
  8. 8Movement disorders Unit, Neurological Institute, Tel Aviv Medical Center, Tel Aviv, Israel
  9. 9Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel
  10. 10Cognitive Neurology Unit, Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel
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Abstract

Background: Neuroimaging with [18F]FDG PET can support the diagnosis of Dementia with Lewy Bodies (DLB), but it remains unclear how genetic factors influence metabolic phenotypes.

Objectives: To determine whether GBA1 and APOE ε4 status are associated with diverging [18F]FDG PET metabolic patterns in DLB.

Methods: We analyzed [18F]FDG PET scans from 43 patients with DLB stratified by GBA1 and APOE ε4 status, and 35 from healthy subjects. Analyses included the cingulate island sign (CIS), regions of interest, SSM/PCA disease patterns, and a machine learning multi-class model. We evaluated the similarity of the DLB patient scans in our cohort with respect to typical DLB, Alzheimer’s disease (AD) and Parkinson’s disease (PD)-like patterns.

Results: APOE ε4 status mainly influenced the CIS, with APOE ε4-negative patients showing greater preservation of the DLB-typical CIS pattern (p = 0.03) compared to APOE ε4 carriers. In contrast, GBA1 status influenced global metabolic phenotype. GBA1 carriers showed a more homogeneous PD/DLB-like metabolic pattern in the machine learning model (p = 0.003) compared to GBA1 non-carriers, whereas the latter group demonstrated greater heterogeneity and higher expression of the AD-related metabolic pattern (p = 0.004). These effects were observed along a metabolic spectrum rather than as distinct clusters.

Conclusions: APOE ε4 and GBA1 modulate distinct aspects of the metabolic phenotype in DLB. GBA1 non-carriers and APOE ε4 carriers showed a higher rate of atypical metabolic signatures, which may contribute to biological heterogeneity and increase the risk of diagnostic misclassification.

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Cite

BibTeXRIS
BibTeX
@article{lovdal2026effect,
  title = {{Effect of genetic factors on [18F]FDG PET metabolic phenotypes in dementia with Lewy bodies}},
  author = {Sofie Lövdal and Sanne K. Meles and Giulia Carli and Anna Dortmond and Rosalie V. Kogan and Orly Goldstein and Mali Gana-Weisz and Rotem I. Orad and Roy N. Alcalay and Noa Bregman and Klaus L. Leenders and Tamara Shiner},
  journal = {European Journal of Nuclear Medicine and Molecular Imaging},
  year = {2026},
  month = aug,
  doi = {10.1007/s00259-026-08124-6},
  url = {https://doi.org/10.1007/s00259-026-08124-6},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Effect of genetic factors on [18F]FDG PET metabolic phenotypes in dementia with Lewy bodies
AU  - Sofie Lövdal
AU  - Sanne K. Meles
AU  - Giulia Carli
AU  - Anna Dortmond
AU  - Rosalie V. Kogan
AU  - Orly Goldstein
AU  - Mali Gana-Weisz
AU  - Rotem I. Orad
AU  - Roy N. Alcalay
AU  - Noa Bregman
AU  - Klaus L. Leenders
AU  - Tamara Shiner
PY  - 2026
DA  - 2026/08/07
JO  - European Journal of Nuclear Medicine and Molecular Imaging
DO  - 10.1007/s00259-026-08124-6
UR  - https://doi.org/10.1007/s00259-026-08124-6
AB  - Background: Neuroimaging with [18F]FDG PET can support the diagnosis of Dementia with Lewy Bodies (DLB), but it remains unclear how genetic factors influence metabolic phenotypes.  Objectives: To determine whether GBA1 and APOE ε4 status are associated with diverging [18F]FDG PET metabolic patterns in DLB.  Methods: We analyzed [18F]FDG PET scans from 43 patients with DLB stratified by GBA1 and APOE ε4 status, and 35 from healthy subjects. Analyses included the cingulate island sign (CIS), regions of interest, SSM/PCA disease patterns, and a machine learning multi-class model. We evaluated the similarity of the DLB patient scans in our cohort with respect to typical DLB, Alzheimer’s disease (AD) and Parkinson’s disease (PD)-like patterns.  Results: APOE ε4 status mainly influenced the CIS, with APOE ε4-negative patients showing greater preservation of the DLB-typical CIS pattern (p = 0.03) compared to APOE ε4 carriers. In contrast, GBA1 status influenced global metabolic phenotype. GBA1 carriers showed a more homogeneous PD/DLB-like metabolic pattern in the machine learning model (p = 0.003) compared to GBA1 non-carriers, whereas the latter group demonstrated greater heterogeneity and higher expression of the AD-related metabolic pattern (p = 0.004). These effects were observed along a metabolic spectrum rather than as distinct clusters.  Conclusions: APOE ε4 and GBA1 modulate distinct aspects of the metabolic phenotype in DLB. GBA1 non-carriers and APOE ε4 carriers showed a higher rate of atypical metabolic signatures, which may contribute to biological heterogeneity and increase the risk of diagnostic misclassification.
SN  - 1619-7070
SN  - 1619-7089
ER  -