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. 2021;18(9):711-720.
doi: 10.2174/1567205018666211126113904.

Heterogeneity of Tau Deposition and Microvascular Involvement in MCI and AD

Annie G Bryant  1 , Mary K Manhard  2 , David H Salat  2 , Bruce R Rosen  2 , Bradley T Hyman  1 , Keith A Johnson  1 , Susie Huang  2 , Rachel E Bennett  1 , Yi-Fen Yen  1
Affiliations

Heterogeneity of Tau Deposition and Microvascular Involvement in MCI and AD

Annie G Bryant et al. Curr Alzheimer Res. 2021.

Abstract

Background: Reduced cerebrovascular function and accumulation of tau pathology are key components of cognitive decline in Alzheimer's disease (AD). Recent multimodal neuroimaging studies show a correlation between cortical tau accumulation and reduced cerebral perfusion. However, animal models predict that tau exerts capillary-level changes that may not be fully captured by standard imaging protocols.

Objective: Using newly-developed magnetic resonance imaging (MRI) technology to measure capillary- specific perfusion parameters, we examined a series of mild cognitive impairment (MCI) and AD patients with tau positron emission tomography (PET) to observe whole-brain capillary perfusion alterations and their association with tau deposition.

Methods: Seven subjects with MCI or AD received Flortaucipir PET to measure tau deposition and spin-echo dynamic susceptibility contrast (SE-DSC) MRI to measure microvascular perfusion (<10μm radius vessels). Gradient-echo (GE) DSC and pseudocontinuous arterial spin labeling (PCASL) MRI were also acquired to assess macrovascular perfusion. Tau PET, microvascular perfusion, and cortical thickness maps were visually inspected in volumetric slices and on cortical surface projections.

Results: High tau PET signal was generally observed in the lateral temporal and parietal cortices, with uptake in the occipital cortex in one subject. Global blood flow measured by PCASL was reduced with increasing tau burden, which was consistent with previous studies. Tau accumulation was spatially associated with variable patterns of microvascular cerebral blood flow (CBF) and oxygen extraction fraction (OEF) in the cortex and with increased capillary transit heterogeneity (CTH) in adjacent periventricular white matter, independent of amyloid-β status.

Conclusion: Although macrovascular perfusion generally correlated with tau deposition at the whole-cortex level, regional changes in microvascular perfusion were not uniformly associated with either tau pathology or cortical atrophy. This work highlights the heterogeneity of AD-related brain changes and the challenges of implementing therapeutic interventions to improve cerebrovascular function.

Keywords: Alzheimer's disease; cerebrovascular function.; dynamic susceptibility contrast magnetic resonance imaging; microvascular perfusion; multimodal neuroimaging; positron emission tomography; tau pathology.

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Figures

Fig. (1)
Fig. (1)
Tau SUVR overlaid on the group-average template structural MRI slices at coronal levels that demonstrate tracer distribution in each case. (A higher resolution / colour version of this figure is available in the electronic copy of the article).
Fig. (2)
Fig. (2)
Representative slices showing FLAIR, tau-PET SUVR, rCBF, rCTH, and rOEF parametric maps for each subject. All volumes are presented in individual subject space. White ovals highlight regions with high tau-PET signal and/or noteworthy SE-DSC microvascular patterns. a.u. = arbitrary units. (A higher resolution / colour version of this figure is available in the electronic copy of the article).
Fig. (3)
Fig. (3)
Tau-PET SUVR, rCBF, rCTH, rOEF, and cortical thickness surface data projected onto the flattened group-average template surface. Left and right hemispheres are indicated with L and R, respectively. a.u. = arbitrary units. (A higher resolution / colour version of this figure is available in the electronic copy of the article).
See this image and copyright information in PMC

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