OLDER HEALTHY PEOPLE HAVE INCREASED VASCULAR PERMEABILITY IN REGIONS SHOWING ‘OFF-TARGET’ [18F]AV-1451 UPTAKE

In older healthy subjects, [18F]AV-1451, which is supposed to bind to hyperphosphorylated tau, also seems to bind to regions (putamen and other nuclei) known not to have abnormal tau deposition on neuropathology. Our aim is to determine whether apparently increased specific [18F]AV-1451 binding in areas unlikely to harbor hyperphosphorylated tau, such as the substantia nigra, globus pallidus and putamen, of older subjects could be related to greater vascular permeability of these regions in older subjects as compared to younger ones. In six younger (23±2.1 years of age, three women) and six older (68.8±7.6 years, three women) healthy subjects we measured dynamic [18F]AV-1451 uptake over a three-hour period. In the same subjects we obtained dynamic gadolinium concentrations before and after a bolus injection of gadolinium, a large molecule commonly used to assess the permeability of the blood-brain barrier, by performing a pre-contrast 3D T1 map (five flip angle acquisitions) followed by a dynamic contrast enhanced MRI (DCE-MRI). During and after infusion, we acquired 180 consecutive T1-weighted volumes (3.4 sec per volume) over 10 minutes. Non-displaceable binding potential (BPND) of [18F]AV-1451 and permeability parameters (Ktrans) of gadolinium were analyzed by volume-of-interest methods and compared using Spearman’s correlation coefficients. There was greater BPND of [18F]AV-1451 in the globus pallidus and putamen (but not in cerebellum or cerebral cortex) of older as compared to younger subjects. Gadolinium Ktrans was similar in the cerebellum, temporal cortex, and choroid plexus of younger and older subjects, but there was higher permeability in the substantia nigra, globus pallidus, and putamen (all p<0.05) of older as compared to younger subjects. Correlations between BPND and Ktrans were significant for substantia nigra, globus pallidus and putamen (all p<0.05). Increased capillary permeability in substantia nigra, pallidum and putamen of healthy older subjects could underlie some of the regional differences in [18F]AV-1451 uptake observed in older as compared to younger healthy subjects.