DOI: 10.1002/alz.078897 ISSN: 1552-5260

Amyloid deposition and neuroinflammation in middle‐aged to older individuals with Down syndrome: a PET evaluation

Laura Cavalcanti de Oliveira, Artur Martins Coutinho, Orestes Vicente Forlenza, Carlos A Buchpiguel, Daniele P de Paula Faria
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology

Abstract

Background

Down syndrome (DS) is characterized by trisomy for chromosome 21 and presents a high incidence and early development of Alzheimer’s disease (AD) (Ram G et al. 2011). The current study aims to evaluate the presence of amyloid in people with DS in different age spans and its correlation with neuroinflammation.

Method

Individuals with DS aged 20‐34 (n = 8), 35‐49 (n = 8), ≥ 50 (n = 4), and cognitively normal individuals without DS (controls n = 11) were evaluated with [11C]PK11195 PET imaging (neuroinflammation) and [11C]PIB PET (β‐amyloid) in a hybrid PET/MRI equipment. The radiopharmaceuticals were administered intravenously (∼370 MBq), and the images were acquired dynamically during 60 min ([11C]PK11195) and 70 min ([11C]PIB). PET images were quantified in the PMOD™ v4.1 software and the results were presented in SUV (Standardized Uptake Value) for [11C]PK11195 and SUVratio with the cerebellum crus as a reference region for [11C]PIB. [11C]PIB images were also visually classified as amyloid positive or negative by an experienced nuclear physician. Statistical analysis was performed by one‐way ANOVA and Bonferroni posthoc, and the differences were considered significant when P≤0.05.

Result

All individuals with DS ≥50 years were amyloid positive and showed increased [11C]PK11195 uptake when compared to younger DS subjects and the control group. Differences were seen particularly in the ≥50 group in the following areas: a) posterior cingulate (1.32±0.05, vs. control = 0.71±0.13, p<0.0001; vs. 20‐34 group = 0.67±0.16, p<0.0001; and 35‐49 group = 0.75±0.14; p = 0.0003); b) amygdala (0.86±0.14, vs. control = 0.62±0.10, p = 0.0450; vs. 20‐34 group = 0.57±0.09, p = 0.0114); c) caudate (0.70±0.12, vs. 20‐34 group = 0.47±0.10, p = 0.0195); d) and thalamus (0.90±0.11, vs. the 20‐34 group = 0.62±0.11, p = 0.0171). [11C]PIB uptake in the posterior cingulate correlated with [11C]PK11195 uptake (r = 0.6201; p = 0.006) in individuals with DS across all age spans.

Conclusion

The increased uptake of [11C]PK11195 in subjects with DS≥ 50 years indicates the presence of a neuroinflammatory process in different brain areas that may be associated with β‐amyloid plaque deposition early in the aging process.

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