Regional association of pCASL-MRI with FDG-PET and PiB-PET in people at risk for autosomal dominant Alzheimer's disease

Neuroimage Clin. 2017 Dec 6;17:751-760. doi: 10.1016/j.nicl.2017.12.003. eCollection 2018.

Abstract

Autosomal dominant Alzheimer's disease (ADAD) is a small subset of Alzheimer's disease that is genetically determined with 100% penetrance. It provides a valuable window into studying the course of pathologic processes that leads to dementia. Arterial spin labeling (ASL) MRI is a potential AD imaging marker that non-invasively measures cerebral perfusion. In this study, we investigated the relationship of cerebral blood flow measured by pseudo-continuous ASL (pCASL) MRI with measures of cerebral metabolism (FDG PET) and amyloid deposition (Pittsburgh Compound B (PiB) PET). Thirty-one participants at risk for ADAD (age 39 ± 13 years, 19 females) were recruited into this study, and 21 of them received both MRI and FDG and PiB PET scans. Considerable variability was observed in regional correlations between ASL-CBF and FDG across subjects. Both regional hypo-perfusion and hypo-metabolism were associated with amyloid deposition. Cross-sectional analyses of each biomarker as a function of the estimated years to expected dementia diagnosis indicated an inverse relationship of both perfusion and glucose metabolism with amyloid deposition during AD development. These findings indicate that neurovascular dysfunction is associated with amyloid pathology, and also indicate that ASL CBF may serve as a sensitive early biomarker for AD. The direct comparison among the three biomarkers provides complementary information for understanding the pathophysiological process of AD.

Keywords: Amyloid deposition; Arterial spin labeling; Autosomal dominant Alzheimer's disease; Cerebral perfusion; FDG pet; Glucose metabolism; MRI; PiB PET.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / genetics
  • Amyloid beta-Protein Precursor / genetics
  • Aniline Compounds / metabolism*
  • Brain / diagnostic imaging*
  • Cerebrovascular Circulation / physiology
  • Cross-Sectional Studies
  • Female
  • Fluorodeoxyglucose F18 / metabolism*
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Positron-Emission Tomography / methods*
  • Presenilin-1 / genetics
  • Presenilin-2
  • Spin Labels
  • Thiazoles / metabolism*
  • Young Adult

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Protein Precursor
  • Aniline Compounds
  • PSEN1 protein, human
  • PSEN2 protein, human
  • Presenilin-1
  • Presenilin-2
  • Spin Labels
  • Thiazoles
  • Fluorodeoxyglucose F18