CenTauR correlation with amyloid, atrophy and cognition across the Alzheimer's Disease spectrum: A tau imaging study with 18F‐MK6240 PET

TL;DR

This study uses tau PET imaging to determine how tau levels in different brain regions relate to amyloid, brain atrophy, and cognitive decline in Alzheimer's disease.

Contribution

The study introduces regional CTR thresholds for tau and clarifies the relationship between tau distribution and Alzheimer's disease progression.

Findings

Cortical tau is rarely found below 60 Centiloid units of amyloid.

Cortical tau strongly correlates with cognitive impairment and brain atrophy.

Tau limited to the MTL is linked to mild memory impairment but not broader cognitive decline.

Abstract

The CenTauR (CTR) standard method for PET measurement of tau provides consistent results across tau tracers. This study establishes regional CTR thresholds for elevated tau and evaluates the CTR relationship with amyloid, neurodegeneration and cognition across the AD spectrum.

924 participants from the AIBL‐ADNeT study (448 cognitively unimpaired (CU), 300 MCI, 176 clinical AD), underwent 18F‐MK6240 tau PET, 18F‐NAV4694 Aβ PET, MRI and cognitive evaluations. We examined the relationship between global and regional tau quantification using the CTR method, and global Aβ (Centiloid), brain atrophy and cognition.

From tau scans in A‐ (<25 CL) CU, 2 SD thresholds were 11 CTR in the mesial temporal lobe (MTL) and 15 CTR in the Temporo‐Parietal (TP) cortex. There was a non‐linear relationship between Aβ and tau with cortical tau rare below 60 CL (Figure 1). In clinical AD, 71% had A+ and neocortical tau+ (TTP+), 14% had neither, 14% had only A+. In MCI, 43% had both, 30% had neither and 26% had only A+. In CU, 64% had neither, 27% were A+T‐, and 7% A+TTP+. However 31% of CU, 68% of MCI and 84% of clinical AD were TMTL+. A‐TMTL+ was observed in 9% of CU, 8% of MCI and 3% of clinical AD (Figure 2). In A+ MCI and AD, cortical tau was strongly inversely associated with age and cortical volume. No association was found with hippocampal volume when tau was limited to the MTL. The most significant factors associated with worse cognition were age and male sex in CU; Aβ, hippocampal volume and tau in MCI, and tau and hippocampal volume in clinical AD. Cortical tau correlated with worse general cognition, while tau limited to the MTL only affected episodic memory. In the absence of tau, Aβ did not correlate with cognitive decline.

This study has established regional CTR thresholds and the prevalence of MTL and cortical tau in CU, MCI and clinical AD. It has confirmed that cortical tau is rarely found below 60 CL of Aβ. Cortical CTR strongly correlates with cognitive impairment and atrophy, while tau restricted to the MTL is linked to mild memory impairment.

Figures