Tau PET imaging with investigational F-18 PI-2620 radiotracer shows sensitivity to early signs of Alzheimer disease in cognitively healthy older adults, according to a study published July 16 in the Journal of Nuclear Medicine.
The finding is from a cross-sectional study of 166 cognitively healthy older adults and 13 younger adults who underwent PET imaging, cognitive testing, and blood biomarker sampling, and points to potential uses in guiding patient selection for tau PET-based Alzheimer disease trials, noted lead author Anne Maass, PhD, of the German Center for Neurodegenerative Diseases in Magdeburg, and colleagues.
“To date, few studies have investigated how F-18 PI-2620 is associated with memory performance or AD-related biomarkers in cognitively unimpaired (CU) older adults,” the authors wrote.
Tau tangles in the medial temporal lobe are common findings in older adults and may contribute to age-related memory decline, the authors noted. F-18 PI-2620 is a second-generation tau PET tracer with high affinity for tau tangles found in Alzheimer disease and other tauopathies.
To further explore the tracer’s potential, the group analyzed dynamic PET scans, MRI, and plasma biomarker samples from 166 cognitively healthy adults (mean age, 72 years old; 44% women; 23% carriers of the APOE4 gene, a known genetic risk factor for Alzheimer disease) and 13 younger adults. The team measured F-18 PI-2620 distribution volume ratio (DVR) in a temporal lobe region tied to Alzheimer pathology and tested its associations with age, sex, APOE4 status, plasma phosphorylated tau 217 (p-tau217), and cognitive test scores spanning memory, language, and other domains.
According to the results, in older adults, temporal F-18 PI-2620 binding was higher in women and APOE4 carriers and was positively associated with plasma p-tau217. A voxelwise analyses showed age-related increases in basal ganglia signal, whereas white matter signal was higher in younger adults.
F-18 PI-2620 average binding potential maps. Mean tracer binding (DVR) image from 165 older adults (A) and 13 young adults (B). Images are scaled from 1 to 1.8 for display purposes, but DVR values of less than 1 were frequently observed. Journal of Nuclear MedicineIn a multiple regression model, higher temporal DVR and lower hippocampal volume predicted worse episodic memory and, together with demographic factors, explained approximately 30% of why memory scores differed from person to person.
“Tau tracer binding was higher in older than young adults and positively associated with female sex, APOE4 genotype, plasma p-tau217, and episodic memory deficits within older adults,” the authors wrote.
The authors noted that to their knowledge, this is the first study of tau PET to include young adults among whom tau accumulation is unlikely, although the small sample size warrants validation. Longitudinal studies incorporating additional neural markers are needed to explain interindividual variability in episodic memory and resilience to brain pathology, the group concluded.
The full study is available here.
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