Longitudinal tau-PET uptake and atrophy in atypical Alzheimer's disease.

Irene Sintini,Val J Lowe,Daniel A Drubach,Mary M Machulda,Clifford R Jack,David S Knopman,Matthew L Senjem,Jennifer L Whitwell,Keith A Josephs,Peter R Martin,Ronald C Petersen,Christopher G Schwarz,Anthony J Spychalla,Jonathan Graff-Radford

doi:10.1016/j.nicl.2019.101823

Irene Sintini, Val J Lowe + Show 12 more

Open Access

https://doi.org/10.1016/j.nicl.2019.101823

Copy DOI

Journal: NeuroImage. Clinical	Publication Date: Jan 1, 2019
Citations: 58	License type: cc-by

Affiliation: Mayo Clinic, Winneshiek Medical Center

Abstract

The aims of this study were: to examine regional rates of change in tau-PET uptake and grey matter volume in atypical Alzheimer's disease (AD); to investigate the role of age in such changes; to describe multimodal regional relationships between tau accumulation and atrophy. Thirty atypical AD patients underwent baseline and one-year follow-up MRI, [18F]AV-1451 PET and PiB PET. Region- and voxel-level rates of tau accumulation and grey matter atrophy relative to cognitively unimpaired individuals, and the influence of age on such rates, were assessed. Univariate and multivariate analyses were performed between baseline measurements and rates of change, between baseline tau and atrophy, and between the two rates of change. Regional patterns of change in tau and volume differed, with highest rates of tau accumulation in frontal lobe and highest rates of atrophy in temporoparietal regions. Age had a negative effect on disease progression, predominantly on tau, with younger patients having a more rapid accumulation. Baseline tau uptake and regions of tau accumulation were disconnected, with high baseline tau uptake across the cortex correlated with high rates of tau accumulation in frontal and sensorimotor regions. In contrast, baseline volume and atrophy were locally related in the occipitoparietal regions. Higher tau uptake at baseline was locally related to higher rates of atrophy in frontal and occipital lobes. Tau accumulation rates positively correlated with rates of atrophy. In summary, our study showed that tau accumulation and atrophy presented different regional patterns in atypical AD, with tau spreading into the frontal lobes while atrophy remains in temporoparietal and occipital cortex, suggesting a temporal disconnect between protein deposition and neurodegeneration.

Highlights

The pathophysiology of Alzheimer's disease (AD) is characterized by neuritic beta-amyloid (Aβ) plaques and tau neurofibrillary tangles (Braak and Braak, 1991; Hyman et al, 2012; Montine et al, 2012)
Estimates of annualized tau standard uptake value ratios (SUVR) changes relative to cognitively unimpaired varied across ROIs in atypical AD, with the smallest changes observed in the hippocampus and greatest changes observed in right middle frontal gyrus, right inferior temporal lobe and right posterior cingulate (SUVR changes > 0.14 per year)
A negative effect of age was found in the majority of the ROIs in atypical AD, and within logopenic progressive aphasia (LPA) and posterior cortical atrophy (PCA)

Summary

Introduction

The pathophysiology of Alzheimer's disease (AD) is characterized by neuritic beta-amyloid (Aβ) plaques and tau neurofibrillary tangles (Braak and Braak, 1991; Hyman et al, 2012; Montine et al, 2012). While Aβ plaques are deposited relatively uniformly throughout the brain (Cho et al, 2016; Iaccarino et al, 2018; Sepulcre et al, 2016), tau neurofibrillary tangles exhibit characteristic topographical patterns at autopsy (Braak and Braak, 1991) that are thought to reflect the neurodegenerative process (Pontecorvo et al, 2017). Autopsy represents the gold standard to quantify tau pathology in the brain, in vivo tau-PET imaging using radiotracers like [18F]AV-1451 that detect tau pathology (Marquie et al, 2015) allows serial measures of tau over time.

Objectives

Methods

Results

Discussion

Conclusion