F-18-florbetapir PET as a marker of myelin integrity across the Alzheimer's disease spectrum

• Purpose Recent evidence suggests that PET imaging with amyloid-beta (A beta) 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 A beta PET, contributes to AD progression remains unexplored. Methods Participants with concurrent F-18-florbetapir (FBP) PET, MRI, and cerebrospinal fluid (CSF) examinations were included (241 cognitively normal, 347 A beta-positive cognitively impaired, and 207 A beta-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 A beta, and WMH burden. Most of these associations were also observed in A beta-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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)

Keyword

F-18-florbetapir

Alzheimer

Myelin

Progression

White matter

white-matter hyperintensities

mild cognitive impairment

amyloid pet

association

pathology

quantification

criteria

decline

lesions

burden

Radiology

Nuclear Medicine & Medical Imaging

Publication and Content Type

ref (subject category)

art (subject category)