Regional Distribution, Asymmetry, and Clinical Correlates of Tau Uptake on [18F]AV-1451 PET in Atypical Alzheimer’s Disease

Abstract

Background: Despite common pathology, Alzheimer’s disease (AD) can have multiple clinical presentations which pathological studies suggest result from differences in the regional distribution of tau pathology. Positron emission tomography (PET) ligands are now available that can detect tau proteins in vivo and hence can be used to investigate the biological mechanisms underlying atypical AD. Objective: To assess regional patterns of tau uptake on PET imaging in two atypical AD variants, posterior cortical atrophy (PCA) and logopenic progressive aphasia (lvPPA). Methods: Eighteen PCA and 19 lvPPA subjects that showed beta-amyloid deposition on PET underwent tau-PET imaging with [18F]AV-1451. Group comparisons of tau uptake in PCA and lvPPA were performed using voxel-level and regional-level analyses. We also assessed the degree of lobar tau asymmetry and correlated regional tau uptake to age and performance on clinical evaluations. Results: Both syndromes showed diffuse tau uptake throughout all cortical regions, although PCA showed greater uptake in occipital regions compared to lvPPA, and lvPPA showed greater uptake in left frontal and temporal regions compared to PCA. While lvPPA showed predominant left-asymmetric tau deposition, PCA was more bilateral. Younger subjects showed greater tau uptake bilaterally in frontal and parietal lobes than older subjects, and sentence repetition, Boston naming test, simultanagnosia and visuoperceptual function showed specific regional tau correlates. Conclusion: Tau deposition is closely related to clinical presentation in atypical AD with age playing a role in determining the degree of cortical tau deposition.

Regional multimodal relationships between tau, hypometabolism, atrophy, and fractional anisotropy in atypical Alzheimer's disease

“…Interestingly, SCCA performed on tau-PET and MRI-volumes and on tau-PET and FDG-PET uptakes selected mostly bilateral or right regions in the first canonical dimension and mostly left regions in the second canonical dimension. This likely reflects the fact that tau uptake and neurodegeneration in atypical AD subjects can be asymmetric (Tetzloff et al, 2018). In contrast, tau deposition was only mildly related to the degeneration of white matter tracts.…”

“…Among these patients, 31 also underwent FDG-PET. All patients underwent a comprehensive neurological evaluation by a Behavioral Neurologist (KAJ or JGR), details of which can be found in a previous study (Tetzloff et al, 2018). The demographic and clinical features of the cohort are shown in Table I.…”

“…Patients with atypical AD can present with impairments in language and in visuospatial/visuoperceptual abilities, executive dysfunction or praxis (Galton, Patterson, Xuereb, & Hodges, 2000). On neuroimaging, atypical AD patients tend to show a relative sparing of the medial temporal lobes compared to typical AD (Galton et al, 2000; Madhavan et al, 2013; Whitwell et al, 2007), and instead show patterns of neurodegeneration and tau uptake affecting the cortex (Jennifer L Whitwell et al, 2018), particularly the temporal, parietal and occipital lobes (Dronse et al, 2017; Nasrallah et al, 2018; Ossenkoppele et al, 2016; Tetzloff et al, 2018; Whitwell et al, 2011; Xia et al, 2017). …”

Asymmetrical atrophy of thalamic subnuclei in Alzheimer's disease and amyloid‐positive mild cognitive impairment is associated with key clinical features

“…In general, the asymmetrical cerebral involvement in AD is considered to be nondirectional, or as Derflinger and colleagues describe it, "asymmetric but not lateralized" [4,5]. However, a number of studies have reported consistent left-lateralized damage in AD, particularly to the hippocampus and white matter integrity [10][11][12][13][14], and also in terms of amyloid and tau pathology [6,15]. Furthermore, the degree of leftward cerebral asymmetry has been associated with disease progression and progressively declining cognitive performance [6,10,13,14].…”

Applications of amyloid, tau, and neuroinflammation PET imaging to Alzheimer's disease and mild cognitive impairment

“…Considering atypical manifestations of AD, those with posterior cortical atrophy display more cortical uptake in occipital areas relative to logopenic progressive aphasia (lvPPA) patients, whilst lvPPA is characterised by more temporal and frontal uptake(Tetzloff et al, 2018). Despite having a favourable pharmacokinetic profile and specificity for tau, further study is required in determining the clinical utility of in vivo imaging using [ 18 F]AV-1451 in AD and MCI(Chien et al, 2014;Zhang et al, 2012).…”