Cross-sectional associations between [18F]GTP1 tau PET and cognition in Alzheimer's disease

Edmond Teng; Michael Ward; Paul T Manser; Sandra Sanabria-Bohorquez; Rebecca D Ray; Kristin R Wildsmith; Suzanne Baker; Geoffrey A Kerchner; Robby M Weimer

doi:10.1016/j.neurobiolaging.2019.05.026

Cross-sectional associations between [¹⁸F]GTP1 tau PET and cognition in Alzheimer's disease

Neurobiol Aging. 2019 Sep:81:138-145. doi: 10.1016/j.neurobiolaging.2019.05.026. Epub 2019 Jun 6.

Authors

Edmond Teng¹, Michael Ward², Paul T Manser³, Sandra Sanabria-Bohorquez⁴, Rebecca D Ray⁵, Kristin R Wildsmith⁶, Suzanne Baker⁷, Geoffrey A Kerchner², Robby M Weimer⁸

Affiliations

¹ Early Clinical Development, Genentech, Inc., South San Francisco, CA, USA. Electronic address: teng.edmond@gene.com.
² Early Clinical Development, Genentech, Inc., South San Francisco, CA, USA.
³ Biostatistics, Genentech, Inc., South San Francisco, CA, USA.
⁴ Clinical Imaging Group, Genentech, Inc., South San Francisco, CA, USA.
⁵ Clinical Imaging Group, Genentech, Inc., South San Francisco, CA, USA; Early Clinical Development Informatics, Genentech, Inc., South San Francisco, CA, USA.
⁶ Biomarker Development, Genentech, Inc., South San Francisco, CA, USA.
⁷ Clinical Imaging Group, Genentech, Inc., South San Francisco, CA, USA; Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
⁸ Department of Biomedical Imaging, Genentech, Inc, South San Francisco, CA, USA.

PMID: 31280117
DOI: 10.1016/j.neurobiolaging.2019.05.026

Abstract

The regional relationships between tau positron emission tomography (PET) imaging and cognitive impairment in Alzheimer's disease (AD) remain uncertain. We examined cross-sectional associations between cognitive performance, cerebral uptake of the novel tau PET tracer [¹⁸F]GTP1, and other neuroimaging indices ([¹⁸F]florbetapir amyloid PET, magnetic resonance imaging) in 71 participants with normal cognition, prodromal AD, or AD dementia. Greater [¹⁸F]GTP1 uptake was seen with increasing clinical severity and correlated with poorer cognition. [¹⁸F]GTP1 uptake and cortical volume (but not [¹⁸F]florbetapir uptake) were independently associated with cognitive performance, particularly within the temporal lobe. Delayed memory was more specifically associated with temporal [¹⁸F]GTP1 uptake; other domains correlated with a broader range of regional [¹⁸F]GTP1 uptake. These data confirm that [¹⁸F]GTP1 tau PET uptake significantly correlates with cognitive performance in AD, but regional correlations between performance in non-memory cognitive domains were less specific than reported by tau PET imaging studies that included participants with atypical focal cortical AD syndromes. Tau PET imaging may have utility as a surrogate biomarker for clinical AD progression in therapeutic trials of disease-modifying interventions.

Keywords: Alzheimer's disease; Clinical trial; Cognition; PET; Tau.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease / diagnostic imaging*
Alzheimer Disease / psychology
Brain / diagnostic imaging*
Brain / metabolism*
Cognition*
Cognitive Dysfunction / diagnostic imaging*
Cognitive Dysfunction / psychology
Cross-Sectional Studies
Female
Fluorine Radioisotopes / metabolism*
Humans
Male
Middle Aged
Neuroimaging
Positron-Emission Tomography*
Radiopharmaceuticals / metabolism*
Severity of Illness Index
tau Proteins / metabolism*

Substances

Fluorine Radioisotopes
Radiopharmaceuticals
tau Proteins
Fluorine-18