Franklin Aigbirhio, United Kingdom
University of Cambridge Clinical NeuroscienceAuthor Of 1 Presentation
SYNAPTIC DENSITY VERSUS TAU ACCUMULATION IN PRIMARY TAUOPATHIES: A NEGATIVE CORRELATION MODERATED BY DISEASE SEVERITY.
Abstract
Aims
The relationship between synaptic loss and tau accumulation in human tauopathies remains to be elucidated in vivo. There is widespread synaptic loss in the primary tauopathies of Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD: amyloid-negative corticobasal syndrome (CBS)) (Holland et al. Mov Disord. 2020).
Methods
We determine how synaptic loss correlates with tau accumulation, using [11C]UCB-J and [18F]AV1451 PET, respectively. Fifteen patients with PSP (m:f 7:8, age ± sd: 71 ± 9.8), fifteen with corticobasal syndrome (9 amyloid negative; m:f 7:2, age ± sd: 70.9 ± 8.2) and fifteen age-/sex-/education-matched healthy controls (m:f 7:8, age ± sd: 68.5 ± 7.5) were recruited. All participants had a neuropsychological battery and a 3T MRI. Patients with CBS also had amyloid PET with [11C]PiB to exclude those with likely Alzheimer’s pathology.
Results
We show that there is a negative correlation between [11C]UCB-J and [18F]AV1451 binding potentials both within regions (pallidum & hippocampus, p<0.05), and between widespread areas of the cortex and striatum. Between-subjects’ variability in the slope of the correlation was related to patients’ disease severity as measured with the PSP rating scale ((F(2,21)=4.13, beta= -0.008, p= <0.01).
Conclusions
We confirm a negative correlation between synaptic density and tau accumulation, moderated by disease severity, however longitudinal imaging is required to estimate the mediation of synaptic loss by tau accumulation. Given the importance of synaptic density for neurocognitive function, our study not only elucidates the pathophysiology of primary tauopathies but also informs the design of clinical trials at different stages of disease.