Table 2.
Preclinical Alzheimer's disease neuroimaging biomarkers.
| Modality | Parameter | Values in preclinical AD | Notes | References |
|---|---|---|---|---|
| rs-fMRI | Paramagnetic property of oxy-hemoglobin/deoxy-hemoglobin in blood flow | Low-frequency spontaneous fluctuation of BOLD signal Reduced functional connectivity | rs-fMRI can detect abnormalities before brain volume loss No regulatory guidelines by FDA or EMA | Machulda et al., 2011; Sheline and Raichle, 2013; Buckley et al., 2017 |
| DTI with sMRI | Diffusion of water molecules in brain | Higher overall mean diffusivity of water molecules Lower fractional anisotropy | Region specificity Detectable abnormality in WM networks in preclinical AD No regulatory guidelines by FDA or EMA |
Sexton et al., 2011; Racine et al., 2014; Fischer et al., 2015; Nedelska et al., 2015 |
| ASL/sMRI | CBF traced by magnetically labeled water molecules | Decreased blood flow in brain | Consistent with vascular hypothesis of AD Could be useful biomarker for tracking disease severity and progression No radiotracer or contrast reagents No regulatory guidelines by FDA or EMA | Alsop et al., 2010; Wang et al., 2013; Wierenga et al., 2014; Hays et al., 2016 |
| Aβ-PET | Radiotracer binding to amyloid beta in specific brain regions | Presence of Aβ detected with 11C-PIB or 18F-labeled amyloid-binding agents | Amyloid accumulation occurs before brain atrophy and is hypothesized to be the first pathological event in AD It is not correlated with AD clinical severity and neurodegeneration Can be used for differential diagnosis per FDA or EMA |
Jack et al., 2009; Jagust et al., 2009; Scheinin et al., 2009; Okamura et al., 2014 |
| 18FDG-PET | Glucose uptake in different brain regions | Glucose uptake using 18FDG | Useful for differential diagnosis of AD and FTD Brain region-specific differentiation capability Can be used for differential diagnosis per FDA or EMA |
Mosconi et al., 2006; Ewers et al., 2013, 2014 |
| Tau-18F-T807-PET | Region specific distribution of tau deposition | 18F-T807 | Progression of AD related to neurodegeneration due to tau deposition | Johnson et al., 2016 |
Aβ, amyloid beta; AD, Alzheimer's disease; ASL MRI, arterial spin-labeled magnetic resonance imaging; BOLD, blood oxygen level-dependent; CBF, cerebral blood flow; DTI, diffusion tensor imaging; EMA, European Medical Agency; FDA, Food and Drug Administration; FTD, frontotemporal dementia; FDG, fluoro-2-deoxy-D-glucose; fMRI, functional MRI; MRI, magnetic resonance imaging; 18F-T807-PET, Fluorinated tau PET ligand; PET, positron emission tomography; PIB, Pittsburgh Compound B; rs-fMRI, resting state functional MRI; sMRI, structural MRI; WM, white matter.