Objective: To evaluate: (1) brain tau pathology in vivo in patients with Progressive Supranuclear Palsy (PSP) and Alzheimer’s disease (AD); (2) whether brain tau pathology (indexed by 18FAV-1451 PET) correlates with disease severity, (3) the feasibility of using [18F]AV-1451 as an in vivo tau biomarker to discriminate between patients with PSP and AD.

Background: In studies of rodent models and ex-vivo AD human brains, the radiotracer [18F]AV-1451 co-localizes with hyper-phosphorylated tau. Here we test whether [18F] AV-1451 reliably differentiates PSP and AD and if it matches the post mortem distribution of tau pathology.

Methods: [18F]AV-1451 PET was used to compare the patterns of tau pathology in n=13 PSP patients, n=9 AD patients, n=6 MCI with positive PiB scan, and 8 controls

Table 1. Participant details.

	PSP (n=13)	AD/MCI+ (n=15)	HCs (n=8)	Group differences
Sex (males/females)	7/6	9/6	3/5	ns
Age, yrs. (mean ± SD)	69.8 (±6.4)	70.8 (±8.7)	64.9 (±8.9)	F=1.3, p=0.25
Education, yrs. (mean ± SD)	11.8 (±1.4)	14.3 (±3.3)	16.0 (±1.6)	F=7.2, p=0.002
MMSE scores (mean ± SD)	25.1 (±5.1)	25.5 (±2.8)	29.8 (±0.4)	F=4.4, p=0.018
ACE-R scores (mean ± SD)	74.5 (±17.1)	75.9 (±11.0)	95.9 (±3.1)	F=7.7, p=0.002

Key to table: SD: standard deviation; PSP: Progressive Supranuclear Palsy; AD/MCI+: Alzheimer Disease/Mild Cognitive impairment (amyloid positive from PiB scanning); HCs: Healthy Controls; ANOVAs: Analyses of Variance; MMSE: Mini Mental State Examination; ACE-R: Addenbrookes’ Cognitive Examination, Revised form. Ns, not significant by Chi-squared test. Group differences by 1-way ANOVA, p-values uncorrected for multiple comparisons.“. Participants underwent cognitive evaluation for memory, language, and visuo-spatial functions. PET data were corrected for partial volume effects and analyzed using ANOVA models for group X region of interest (ROI) interactions. Correlations between [18F]AV-1451 SUVR and disease severity were studied using multiple regression models. Age and education were included as covariates of no interest. Finally, to assess whether [18F]AV-1451 uptake could distinguish PSP patients from AD cases, subject-specific [18F]AV-1451 data per each ROI were input as key features in a multivariate supervised support vector machine (SVM) analysis.

Results: Relative to controls, both PSP and AD groups showed elevated [18F] AV-1451 binding, but in very different locations . PSP patients displayed increased [18F]AV-1451 uptake in the midbrain and pallidum, consistent with post mortem studies. AD patients showed increased [18F]AV-1451 uptake in the hippocampus, amygdala, and other medial temporal lobe areas as well as extensive cortical regions. No significant correlations between [18F]AV-1451 uptake in any ROI and clinical and neuropsychological measures of disease severity were identified. SVM analyses showed that the binding of [18F]AV-1451 in the midbrain and hippocampus separated PSP from AD groups with an accuracy of 96%.

Conclusions: Our results suggest that [18F]AV-1451 PET is a useful in vivo tool to assess brain tau pathology in PSP and AD. [18F]AV-1451 may improve the diagnostic protocols in PSP and AD and be a useful outcome measure in trials that aim to halt the tau-related neurodegenerative disorders.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/18fav-1451-pet-imaging-of-tau-in-progressive-supranuclear-palsy-and-alzheimers-disease/