In vivo measures of tau burden are associated with atrophy in early Braak stage medial temporal lobe regions in amyloid-negative individuals

Sandhitsu R Das; Long Xie; Laura E M Wisse; Nicolas Vergnet; Ranjit Ittyerah; Salena Cui; Paul A Yushkevich; David A Wolk; Alzheimer's Disease Neuroimaging Initiative

doi:10.1016/j.jalz.2019.05.009

In vivo measures of tau burden are associated with atrophy in early Braak stage medial temporal lobe regions in amyloid-negative individuals

Alzheimers Dement. 2019 Oct;15(10):1286-1295. doi: 10.1016/j.jalz.2019.05.009. Epub 2019 Sep 6.

Authors

Sandhitsu R Das¹, Long Xie², Laura E M Wisse³, Nicolas Vergnet⁴, Ranjit Ittyerah², Salena Cui⁵, Paul A Yushkevich⁶, David A Wolk⁷; Alzheimer's Disease Neuroimaging Initiative

Affiliations

¹ Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA; Penn Image Computing and Science Laboratory, University of Pennsylvania, Philadelphia, PA, USA; Penn Memory Center, University of Pennsylvania, Philadelphia, PA, USA; Penn Alzheimer's Disease Core Center, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: [email protected].
² Penn Image Computing and Science Laboratory, University of Pennsylvania, Philadelphia, PA, USA; Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
³ Penn Image Computing and Science Laboratory, University of Pennsylvania, Philadelphia, PA, USA; Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA; Penn Memory Center, University of Pennsylvania, Philadelphia, PA, USA.
⁴ Penn Image Computing and Science Laboratory, University of Pennsylvania, Philadelphia, PA, USA.
⁵ Jefferson University, Philadelphia, PA, USA.
⁶ Penn Image Computing and Science Laboratory, University of Pennsylvania, Philadelphia, PA, USA; Penn Alzheimer's Disease Core Center, University of Pennsylvania, Philadelphia, PA, USA; Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
⁷ Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA; Penn Memory Center, University of Pennsylvania, Philadelphia, PA, USA; Penn Alzheimer's Disease Core Center, University of Pennsylvania, Philadelphia, PA, USA.

Abstract

Introduction: It is unclear the degree to which tau pathology in the medial temporal lobe (MTL) measured by ¹⁸F-flortaucipir positron emission tomography relates to MTL subregional atrophy and whether this relationship differs between amyloid-β-positive and amyloid-β-negative individuals.

Methods: We analyzed correlation of MTL ¹⁸F-flortaucipir uptake with MTL subregional atrophy measured with high-resolution magnetic resonance imaging in a region of interest and regional thickness analysis and determined the relationship between memory performance and positron emission tomography and magnetic resonance imaging measures.

Results: Both groups showed strong correlations between ¹⁸F-flortaucipir uptake and atrophy, with similar spatial patterns. Effects in the rhinal cortex recapitulated Braak staging. Correlations of memory recall with atrophy and tracer uptake were observed.

Discussion: Correlation patterns between tau burden and atrophy in the amyloid-β-negative group mimicking early Braak stages suggests that ¹⁸F-flortaucipir is sensitive to tau pathology in primary age-related tauopathy. Correlations of imaging measures with memory performance indicate that this pathology is associated with poorer cognition.

Keywords: (18)F-flortaucipir; AV1451; Amyloid negative; Amyloid positive; Atrophy; Braak stages; Logical memory; Medial temporal lobe; Subfield; Subregion; Tau PET; Volume.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Aged
Alzheimer Disease / diagnostic imaging
Alzheimer Disease / metabolism
Amyloid / metabolism*
Atrophy / metabolism*
Carbolines
Cognitive Dysfunction / diagnostic imaging
Cognitive Dysfunction / metabolism
Female
Humans
Magnetic Resonance Imaging
Male
Memory / physiology
Neuropsychological Tests / statistics & numerical data
Positron-Emission Tomography
Tauopathies / metabolism*
Temporal Lobe / metabolism*
tau Proteins / metabolism*

Substances

Amyloid
Carbolines
tau Proteins
7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole

Abstract

Publication types

MeSH terms

Substances

Grants and funding