RT Journal Article SR Electronic T1 Low PiB PET retention in presence of pathologic CSF biomarkers in Arctic APP mutation carriers JF Neurology JO Neurology FD Lippincott Williams & Wilkins SP 229 OP 236 DO 10.1212/WNL.0b013e31825fdf18 VO 79 IS 3 A1 Michael Schöll A1 Anders Wall A1 Steinunn Thordardottir A1 Daniel Ferreira A1 Nenad Bogdanovic A1 Bengt Långström A1 Ove Almkvist A1 Caroline Graff A1 Agneta Nordberg YR 2012 UL http://n.neurology.org/content/79/3/229.abstract AB Objective: To investigate the particular pathology of the Arctic APP (APParc) early-onset familial Alzheimer disease (eoFAD) mutation for the first time in vivo with PET in comparison with other eoFAD mutations and sporadic Alzheimer disease (sAD). Methods: We examined 2 APParc mutation carriers together with 5 noncarrier siblings cross-sectionally with 11C-labeled Pittsburgh compound B (PiB) and 18F-fluorodeoxyglucose (FDG) PET, as well as MRI, CSF biomarkers, and neuropsychological tests. Likewise, we examined 7 patients with sAD, 1 carrier of a presenilin 1 (PSEN1) mutation, 1 carrier of the Swedish APP (APPswe) mutation, and 7 healthy controls (HCs). Results: Cortical PiB retention was very low in the APParc mutation carriers while cerebral glucose metabolism and CSF levels of Aβ1-42, total and phosphorylated tau were clearly pathologic. This was in contrast to the PSEN1 and APPswe mutation carriers revealing high PiB retention in the cortex and the striatum in combination with abnormal glucose metabolism and CSF biomarkers, and the patients with sAD who showed typically high cortical PiB retention and pathologic CSF levels as well as decreased glucose metabolism when compared with HCs. Conclusions: The lack of fibrillar β-amyloid (Aβ) as visualized by PiB PET in APParc mutation carriers suggests, given the reduced glucose metabolism and levels of Aβ1-42 in CSF, that other forms of Aβ such as oligomers and protofibrils are important for the pathologic processes leading to clinical Alzheimer disease. Aβ=β-amyloid; AD=Alzheimer disease; APParc=Arctic APP; APPswe=Swedish APP mutation carrier; CAA=cerebral amyloid angiopathy; eoFAD=early-onset familial Alzheimer disease; FDG=18F-fluorodeoxyglucose; MCI=mild cognitive impairment; MMSE=Mini-Mental State Examination; p-tau=phosphorylated tau; PiB=Pittsburgh compound B; sAD=sporadic Alzheimer disease; t-tau=total tau; varAD=variant AD