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 (11)C-labeled Pittsburgh compound B (PiB) and (18)F-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 Aβ(1-42), 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 Aβ(1-42) in CSF, that other forms of Aβ such as oligomers and protofibrils are important for the pathologic processes leading to clinical Alzheimer disease.
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 (11)C-labeled Pittsburgh compound B (PiB) and (18)F-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 Aβ(1-42), 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 Aβ(1-42) in CSF, that other forms of Aβ such as oligomers and protofibrils are important for the pathologic processes leading to clinical Alzheimer disease.
Authors: Gaël Chételat; Rik Ossenkoppele; Victor L Villemagne; Audrey Perrotin; Brigitte Landeau; Florence Mézenge; William J Jagust; Vincent Dore; Bruce L Miller; Stéphanie Egret; William W Seeley; Wiesje M van der Flier; Renaud La Joie; David Ames; Bart N M van Berckel; Philip Scheltens; Frederik Barkhof; Christopher C Rowe; Colin L Masters; Vincent de La Sayette; Femke Bouwman; Gil D Rabinovici Journal: Brain Date: 2016-06-29 Impact factor: 13.501
Authors: Sylvia E Perez; Jennifer C Miguel; Bin He; Michael Malek-Ahmadi; Eric E Abrahamson; Milos D Ikonomovic; Ira Lott; Eric Doran; Melissa J Alldred; Stephen D Ginsberg; Elliott J Mufson Journal: Acta Neuropathol Date: 2019-02-07 Impact factor: 17.088
Authors: Marissa D Zwan; Juha O Rinne; Steen G Hasselbalch; Agneta Nordberg; Alberto Lleó; Sanna-Kaisa Herukka; Hilkka Soininen; Ian Law; Justyna M C Bahl; Stephen F Carter; Juan Fortea; Rafael Blesa; Charlotte E Teunissen; Femke H Bouwman; Bart N M van Berckel; Pieter J Visser Journal: Neurology Date: 2015-10-14 Impact factor: 9.910