Low PiB PET retention in presence of pathologic CSF biomarkers in Arctic APP mutation carriers.
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.
Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Stockholm, Sweden.
Michael
M
Schöll
Anders
A
Wall
Steinunn
S
Thordardottir
Daniel
D
Ferreira
Nenad
N
Bogdanovic
Bengt
B
Långström
Ove
O
Almkvist
Caroline
C
Graff
Agneta
A
Nordberg
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000235:genetics*; D000814:Aniline Compounds; D001284:Atrophy; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D002250:Carbon Radioisotopes; D003071:Cognition / Q000502:physiology; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D053764:Presenilin-1 / Q000235:genetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D013844:Thiazoles; D016875:tau Proteins / Q000134:cerebrospinal fluid
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D015415:Biomarkers; D002250:Carbon Radioisotopes; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; D019275:Radiopharmaceuticals; D013844:Thiazoles; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D019788:Fluorodeoxyglucose F18