Cortical and substantia nigra 18F‐PI‐2620 tau PET signal in Lewy body disease

Abstract

AbstractBackgroundTau PET imaging is a potential tool for measuring comorbid tau pathology in patients with Lewy body disease. Furthermore, tau PET ligands are known to bind to neuromelanin within substantia nigra (SN), with reduced binding in Parkinson’s disease relative to healthy individuals. We sought to characterize 18F‐PI‐2620, a next generation PET tracer, in patients from across the Lewy body disease spectrum.MethodA total of 126 participants from the Stanford Alzheimer’s Disease Center (ADRC) and the Stanford Aging and Memory Study (SAMS) were recruited for PET scanning with 18F‐PI‐2620. We compared 18F‐PI‐2620 uptake within medial temporal (entorhinal cortex, amygdala) and occipital (precuneus, lingual gyrus) regions as well as SN across patients with Parkinson’s disease (PD, n = 26), dementia with Lewy bodies (DLB, n = 6), and Alzheimer’s disease spectrum (AD, n = 21), in addition to cognitively normal older adults (healthy controls, HC, n = 73). Mean bilateral signal was extracted from cortical regions of interest in native space 18F‐PI‐2620 SUVRs (inferior cerebellar gray reference). Amyloid status was determined either by 18F‐florbetaben PET or CSF. To quantify SN, SUVRs were normalized to template space and an anatomical mask was used to extract mean signal. MDS‐UPDRS‐III motor exam scores, collected in an off‐medication state for all patients, were used as a measure of motor impairment.ResultEntorhinal and amygdala SUVR were significantly elevated in the AD group relative to all other groups, and in amyloid‐positive relative to amyloid‐negative HC (Fig 1). Tau burden in all regions was low across PD and DLB groups and did not differ based on amyloid status. SN SUVR was significantly lower in the PD group compared to the HC and AD group (Fig 2A). In patients with Lewy body disease (PD & DLB), MDS‐UPDRS‐III scores were negatively associated with SN SUVR (Fig 2B).ConclusionThese findings suggest that cortical tau is low in Lewy body disease. Neuromelanin‐related 18F‐PI‐2620 signal within SN carries information about disease severity. Cortical tau and SN binding represent two unique signals in the same tau PET image that may be informative in the context of Lewy body disease.