Down syndrome (DS) is a genetic form of Alzheimer’s disease (AD). Due to the overexpression of the APP gene on chromosome 21, nearly all individuals with DS develop AD-related pathological changes and dementia secondary to this disease. Brain metabolism, measured using fluorodeoxyglucose positron emission tomography ([¹⁸F]FDG-PET), is considered a biomarker of AD-related neurodegeneration. This recent study published in Annals of Neurology analyzed how brain metabolism varies in adults with DS along the AD continuum and its relationship with cerebrospinal fluid (CSF) biomarkers.
What was done in this study?
The study included 105 adults with DS at different stages of AD (asymptomatic, prodromal, and dementia) and 71 cognitively healthy euploid controls. FDG-PET images and CSF biomarkers (Aβ42/40, phosphorylated tau, and neurofilaments) were analyzed. The study evaluated the influence of sociodemographic variables, clinical stages of AD, and CSF biomarkers on brain metabolism.
Key Findings
- Hypometabolism pattern in DS: Compared to controls, individuals with DS showed global hypometabolism, even in the asymptomatic stage, primarily affecting frontal and parietal regions.
- Progression of AD in DS: Hypometabolism in the prodromal stage was predominant in medial parietal regions and extended to the rest of the temporoparietal regions and frontal areas in the dementia stage.
- Relationship with CSF biomarkers: All three biomarkers showed a strong association with hypometabolism in AD-affected regions in participants with DS, with the most significant correlation observed with neurofilament light chain (NfL) levels.
Study Relevance
This study reinforces the value of [¹⁸F]FDG-PET in detecting AD-related neurodegeneration in DS, even in the preclinical stage. The findings could have implications for selecting patients for clinical trials of disease-modifying therapies and for monitoring disease progression, which will need to be confirmed in future longitudinal studies.