Authors: Mackenzie L Carlson, Tyler Toueg, Nicole Corso, Mehdi Khalighi, Phillip DiGiacomo, Greg Zaharchuk, Michelle L James, Michael D Greicius, Elizabeth C Mormino, Michael Zeineh
Published: 2020-12-07
DOI: 10.1002/alz.045305
Source: Full article
AbstractBackgroundMicrostructural tissue alterations in Alzheimer disease (AD) contribute to decreased fractional anisotropy (FA) in white matter (Sexton et al. 2011), which may be secondary to tau‐based neurodegeneration that starts in the medial temporal lobe (MTL). Here, we show that tau accumulation in the entorhinal and perirhinal cortices (ERC/PRC) – the first area of the MTL known to accumulate tau pathology (Braak & Braak, 1991) – correlates with parahippocampal gyral FA, and both are altered in AD and mild cognitive impairment (MCI) compared with control subjects.Method21 subjects, 5 amyloid‐positive AD (3 amnestic), 5 amyloid‐positive MCI (4 amnestic), and 11 healthy control, underwent a dynamic 90‐minute tau‐PET scan on a 3T PET‐MR after 5mCi intravenous injection of PI‐2620 (Life Molecular Imaging, Inc.). During the PET acquisition, coronal‐oblique T2‐weighted fast‐spin‐echo (TR 14111ms, TE 102.4ms, FA 111, 0.43x0.43x1.9mm resolution, 3m24s) and DTI (6b=0 s/mm2, 60 b=1000s/mm2 directions, 1.6‐2.0mm isotropic) were acquired. Standardized uptake value ratio (SUVr) maps from 60‐90 were normalized to the inferior cerebellar cortex. DTI and PET were registered to coronal T2 MR image space. Hippocampal subfields (CA1, dentate gyrus and CA2‐4 (DG), subiculum, entorhinal/perirhinal cortex, and parahippocampal gyrus) were segmented using Automated Segmentation of Hippocampal Subfields (Yushkevich et al, 2010) with a tailored atlas (Parivash et al, 2019). Mean subfield SUVr and FA were computed after subfields were 1‐voxel 2D‐eroded in the coronal‐oblique plane. Statistics utilized a linear regression model correcting for age.ResultSUVr differences were present between amnestic AD/MCI (N=7) and controls (N=11) in the ERC/PRC (p<0.001), more than in other subfields (Figure 1A). Amnestic AD/MCI demonstrated significantly lower FA than controls in the parahippocampal gyrus (p =0.04) (Figure 1B). FA in the parahippocampal gyrus correlates strongly (R=‐0.60) with ERC/PRC tau SUVr in amnestic AD, amnestic MCI, and controls and shows clear clustering by subject group (Figure 2).ConclusionThe correlation between parahippocampal FA and tau SUVr in the ERC/PRC indicate that simultaneous in vivo PET/MRI measurements of early‐stage tau accumulation and white matter degradation may be useful to interrogate the relationship between tau accumulation and MTL white matter microstructure.