MRI and flortaucipir relationships in Alzheimer's phenotypes are heterogeneous

Josephs, Keith A.; Tosakulwong, Nirubol; Graff‐Radford, Jonathan; Weigand, Stephen D.; Buciuc, Marina; Machulda, Mary M.; Jones, David T.; Schwarz, Christopher G.; Senjem, Matthew L.; Ertekin-Taner, Nilüfer; Kantarci, Kejal; Boeve, Bradley F.; Knopman, David S.; Jack, Clifford R.; Petersen, Ronald C.; Lowe, Val J.; Whitwell, Jennifer L.

doi:10.1002/acn3.51038

Cited by 17 publications

(24 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This evolution is similar (though not identical) to Braak neuropathologic staging of tau neurofibrillary tangles and closely colocalizes with brain atrophy and hypometabolism patterns as measured by MRI or 18 F-FDG PET (3,9). Increasing spread of tau is associated with clinical impairment (10)(11)(12), with the tau PET binding topography associated with domain-specific cognitive deficits (13,14) and distinct AD clinical variants (9,15,16),…”

supporting

confidence: 51%

Tau Beats Amyloid in Predicting Brain Atrophy in Alzheimer Disease: Implications for Prognosis and Clinical Trials

2022

View full text Add to dashboard Cite

Sever al biomarkers have emerged in the past few decades to quantify pathologic brain changes related to Alzheimer disease (AD). In particular, PET radiotracers that bind selectively to amyloid-b plaques and tau neurofibrillary tangles have advanced AD research and drug development by enabling the detection and quantification of the neuropathologic lesions that define AD in living people.Among amyloid-b PET tracers, 11 C-Pittsburgh compound B was the first to be developed, followed by 18 F-labeled tracers approved for clinical use (i.e., 18 F-florbetapir, 18 F-florbetaben, and 18

show abstract

supporting

confidence: 51%

Tau Beats Amyloid in Predicting Brain Atrophy in Alzheimer Disease: Implications for Prognosis and Clinical Trials

2022

View full text Add to dashboard Cite

show abstract

“…As hypothesized: (a) from a biological perspective , different tau-PET patterns revealed a differential association with longitudinal atrophy; and (b) from a methodological perspective , characterizing heterogeneity on a continuous scale may be more useful than the conventional categorization of individuals into discrete patterns. Recent studies have investigated the association between tau pathology and downstream neurodegeneration in healthy, cognitively normal, prodromal AD, and AD dementia [ 5 , 7 – 9 , 36 – 38 ] individuals, as well as in clinical subtypes of AD [ 39 – 41 ]. To our knowledge, our study is the first to characterize the role of biological heterogeneity (tau-PET patterns) as a modulator of the association between tau pathology and neurodegeneration.…”

Section: Discussionmentioning

confidence: 99%

Associations between different tau-PET patterns and longitudinal atrophy in the Alzheimer’s disease continuum: biological and methodological perspectives from disease heterogeneity

et al. 2023

View full text Add to dashboard Cite

Background Subtypes and patterns are defined using tau-PET (tau pathology) and structural MRI (atrophy) in Alzheimer’s disease (AD). However, the relationship between tau pathology and atrophy across these subtypes/patterns remains unclear. Therefore, we investigated the biological association between baseline tau-PET patterns and longitudinal atrophy in the AD continuum; and the methodological characterization of heterogeneity as a continuous phenomenon over the conventional discrete subgrouping. Methods In 366 individuals (amyloid-beta-positive cognitively normal, prodromal AD, AD dementia; amyloid-beta-negative cognitively normal), we examined the association between tau-PET patterns and longitudinal MRI. We modeled tau-PET patterns as a (a) continuous phenomenon with key dimensions: typicality and severity; and (b) discrete phenomenon by categorization into patterns: typical, limbic predominant, cortical predominant and minimal tau. Tau-PET patterns and associated longitudinal atrophy were contextualized within the Amyloid/Tau/Neurodegeneration (A/T/N) biomarker scheme. Results Localization and longitudinal atrophy change vary differentially across different tau-PET patterns in the AD continuum. Atrophy, a downstream event, did not always follow a topography akin to the corresponding tau-PET pattern. Further, heterogeneity as a continuous phenomenon offered an alternative and useful characterization, sharing correspondence with the conventional subgrouping. Tau-PET patterns also show differential A/T/N profiles. Conclusions The site and rate of atrophy are different across the tau-PET patterns. Heterogeneity should be treated as a continuous, not discrete, phenomenon for greater sensitivity. Pattern-specific A/T/N profiles highlight differential multimodal interactions underlying heterogeneity. Therefore, tracking multimodal interactions among biomarkers longitudinally, modeling disease heterogeneity as a continuous phenomenon, and examining heterogeneity across the AD continuum could offer avenues for precision medicine.

show abstract

“…As hypothesized: (a) different tau-PET patterns revealed a differential association with longitudinal atrophy; and (b) characterizing patterns on a continuous-scale may be more sensitive than the conventional categorization of individuals into discrete patterns. Recent studies have investigated the association between tau pathology and downstream neurodegeneration in healthy, cognitively normal, prodromal AD, and AD dementia [5][6][7][8][24][25][26] individuals, as well as in clinical subtypes of AD [27][28][29]. To our knowledge, our study is the first to characterize this association relative to the biological heterogeneity [16] (tau-PET patterns) within the AD continuum.…”

Section: Discussionmentioning

confidence: 88%

Associations between different tau-PET patterns and longitudinal atrophy in the Alzheimer’s disease continuum

Mohanty¹,

Ferreira²,

Nordberg

et al. 2021

Preprint

View full text Add to dashboard Cite

INTRODUCTION: Different subtypes/patterns have been defined using tau-PET and structural-MRI in Alzheimer's disease (AD), but the relationship between tau pathology and atrophy remains unclear. Our goals were twofold: (a) investigate the association between baseline tau-PET patterns and longitudinal atrophy in the AD continuum; (b) characterize heterogeneity as a continuous phenomenon over the conventional notion using discrete subgroups. METHODS: In 366 individuals (amyloid-beta-positive: cognitively normal, prodromal AD, AD dementia; amyloid-beta-negative healthy), we examined the association between tau-PET patterns (operationalized as a continuous phenomenon and a discrete phenomenon) and longitudinal sMRI. RESULTS: We observed a differential association between tau-PET patterns and longitudinal atrophy. Heterogeneity, measured continuously, may offer an alternative characterization, sharing correspondence with the conventional subgrouping. DISCUSSION: Site and the rate of atrophy are modulated differentially by tau-PET patterns in the AD continuum. We postulate that heterogeneity be treated as a continuous phenomenon for greater sensitivity over the current/conventional discrete subgrouping.

show abstract

MRI and flortaucipir relationships in Alzheimer's phenotypes are heterogeneous

Cited by 17 publications

References 50 publications

Tau Beats Amyloid in Predicting Brain Atrophy in Alzheimer Disease: Implications for Prognosis and Clinical Trials

Tau Beats Amyloid in Predicting Brain Atrophy in Alzheimer Disease: Implications for Prognosis and Clinical Trials

Associations between different tau-PET patterns and longitudinal atrophy in the Alzheimer’s disease continuum: biological and methodological perspectives from disease heterogeneity

Associations between different tau-PET patterns and longitudinal atrophy in the Alzheimer’s disease continuum

Contact Info

Product

Resources

About