RT Journal Article
T1 18F-florbetapir PET as a marker of myelin integrity across the Alzheimer’s disease spectrum
A1 Moscoso Rial, Alexis
A1 Silva Rodríguez, Jesús
A1 Aldrey Vázquez, José Manuel
A1 Cortés Hernández, Julia
A1 Pías Peleteiro, Juan Manuel
A1 Ruibal Morell, Álvaro
A1 Aguiar Fernández, Pablo
K1 18F-florbetapir
K1 Alzheimer
K1 Myelin
K1 Progression
K1 White matter
AB Purpose: Recent evidence suggests that PET imaging with amyloid-β (Aβ) tracers can be used to assess myelin integrity in cerebral white matter (WM). Alzheimer’s disease (AD) is characterized by myelin changes that are believed to occur early in the disease course. Nevertheless, the extent to which demyelination, as measured with Aβ PET, contributes to AD progression remains unexplored. Methods: Participants with concurrent 18F-florbetapir (FBP) PET, MRI, and cerebrospinal fluid (CSF) examinations were included (241 cognitively normal, 347 Aβ-positive cognitively impaired, and 207 Aβ-negative cognitively impaired subjects). A subset of these participants had also available diffusion tensor imaging (DTI) images (n = 195). We investigated cross-sectional associations of FBP retention in the white matter (WM) with MRI-based markers of WM degeneration, AD clinical progression, and fluid biomarkers. In longitudinal analyses, we used linear mixed models to assess whether FBP retention in normal-appearing WM (NAWM) predicted progression of WM hyperintensity (WMH) burden and clinical decline. Results: In AD-continuum individuals, FBP retention in NAWM was (1) higher compared with WMH regions, (2) associated with DTI-based measures of WM integrity, and (3) associated with longitudinal progression of WMH burden. FBP uptake in WM decreased across the AD continuum and with increasingly abnormal CSF biomarkers of AD. Furthermore, FBP retention in the WM was associated with large-calibre axon degeneration as reflected by abnormal plasma neurofilament light chain levels. Low FBP uptake in NAWM predicted clinical decline in preclinical and prodromal AD, independent of demographics, global cortical Aβ, and WMH burden. Most of these associations were also observed in Aβ-negative cognitively impaired individuals. Conclusion: These results support the hypothesis that FBP retention in the WM is myelin-related. Demyelination levels progressed across the AD continuum and were associated with clinical progression at early stages, suggesting that this pathologic process might be a relevant degenerative feature in the disease course
PB Springer
YR 2022
FD 2022
LK http://hdl.handle.net/10347/28997
UL http://hdl.handle.net/10347/28997
LA eng
NO European Journal of Nuclear Medicine and Molecular Imaging 49, 1242–1253 (2022). https://doi.org/10.1007/s00259-021-05493-y
NO Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was partially supported by the projects RYC-2015/17430 (Ramón y Cajal, Pablo Aguiar), PI19/01315 (ISCIII project), 0624_2IQBIONEURO_6_E and EAPA_791/2018 (UE projects)
DS Minerva
RD 30 abr 2026