O1‐01‐05: [18f]flutemetamol Amyloid Pet in Symptomatic Alzheimer's Disease (Ad) and Pathologically Preclinical Ad (P‐pread) in Comparison to Non‐ad Controls: Impact of Cerebral Amyloid Angiopathy

The deposition of the amyloid β-protein (Aβ) in the brain is a hallmark lesion of AD. Aβ is seen in amyloid plaques in the neuropil and in the vessel wall of cerebral amyloid angiopathy (CAA)-affected blood vessels. Amyloid PET imaging provides information about the presence and distribution of Aβ pathology of patients. [18 F]Flutemetamol is one tracer approved in the US for amyloid PET imaging in patients being evaluated for AD or other dementias. However, until now it is not clear whether CAA has relation to amyloid PET imaging in addition to amyloid plaque pathology. To analyze the development of Aβ pathology and its relation to amyloid PET imaging we studied a cohort of 68 autopsy brains of patients participating in this [18 F]flutemetamol amyloid PET imaging end of life study (GE067-007). Image quantitation via standard uptake volume ratio (SUVR) measurements was performed in the cortex. At autopsy we classified the brains neuropathologically and determined the phases of Aβ deposition in the brain as recommended by the National Institute of Aging-Alzheimer Association guidelines for the neuropathological diagnosis of AD. Stages of CAA distribution and type of CAA (capillary vs. non-capillary CAA) were determined neuropathologically. We found that in the first stages of pathologically defined preclinical AD (p-preAD) exhibiting Aβ phases 1 and 2, amyloid PET cortex SUVRs did not differ from that of non-AD cases. Slightly increased SUVR-levels were observed in the cortex of Aβ phase 3 p-preAD cases. A further, highly significant increase was seen in symptomatic AD cases correlating Aβ pathology with the diagnosis of AD. CAA, regardless of the type, correlated with amyloid plaque pathology but did not influence the cortical SUVR levels independently. Moreover, a single case with severe CAA in the occipital cortex in the absence of cortical plaques did not show significantly increased SUVR-levels. [18 F]flutemetamol amyloid PET shows promise to aid in detection of symptomatic AD whereas few p-preAD cases with already advanced amyloid plaque pathology could be identified. CAA, thereby, was not related to a false positive pattern in [18 F]flutemetamol amyloid PET.