title: PET amyloid ligand [11C]PIB uptake shows predominantly striatal increase in variant Alzheimer's disease.
abstract: Variant Alzheimer's disease (VarAD) with spastic paraparesis and presenile dementia is associated with certain mutations of the presenilin 1 (PS-1) gene, particularly those leading to deletion of exon 9 (PS-1Delta E9). VarAD is neuropathologically characterized by the presence of unusually large, Abeta42 positive, non-cored 'cotton wool' plaques (CWPs), also devoid of dystrophic neurites. The aim of the present study was to find out whether [(11)C]PIB would show increased uptake and serve as an in vivo biomarker of amyloid accumulation in VarAD. A further aim was to assess the correspondence of the [(11)C]PIB binding to the amount and type of Abeta deposits in another group of deceased VarAD patients' brains. We studied four patients with VarAD and eight healthy controls with PET using [(11)C]PIB as tracer. Parametric images were computed by calculating the region-to-cerebellum and region-to-pons ratio in each voxel over 60-90 min. Group differences in [(11)C]PIB uptake were analysed with automated region-of-interest (ROI) analysis. [(11)C]PIB uptake was compared to the immunohistochemically demonstrated deposition of Abeta in the brains of another group of four deceased VarAD patients. Patients with VarAD had significantly higher [(11)C] PIB uptake than the control group in the striatum (caudate nucleus and putamen), anterior and posterior cingulate gyrus, occipital cortex and thalamus. In the caudate and putamen [(11)C]PIB uptake, expressed as region-to-cerebellum ratio, was on the average 43% greater than the mean of the control group. The increases in the anterior (28%) and posterior (27%) cingulate gyrus, occipital cortex (21%) and thalamus (14%) were smaller. All VarAD patients showed this similar topographical pattern of increased [(11)C]PIB uptake. The results were essentially similar when the uptake was expressed as region-to-pons ratios. [(11)C]PIB imaging shows increased uptake in patients with VarAD especially in the striatum, and it can be used to detect amyloid accumulation in vivo in these patients. The pattern of increased [(11)C]PIB uptake is different from that described in sporadic Alzheimer's disease and resembles that seen in Alzheimer's disease patients with certain presenilin-1 mutations or amyloid precursor protein gene duplication showing predominantly striatal increase in [(11)C]PIB uptake.
authors.affiliation: Turku PET Centre, University of Turku, PO Box 52, 20521 Turku, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Koivunen
authors.forename: A
authors.initials: A
authors.lastname: Verkkoniemi
authors.forename: S
authors.initials: S
authors.lastname: Aalto
authors.forename: A
authors.initials: A
authors.lastname: Paetau
authors.forename: J-P
authors.initials: JP
authors.lastname: Ahonen
authors.forename: M
authors.initials: M
authors.lastname: Viitanen
authors.forename: K
authors.initials: K
authors.lastname: Någren
authors.forename: J
authors.initials: J
authors.lastname: Rokka
authors.forename: M
authors.initials: M
authors.lastname: Haaparanta
authors.forename: H
authors.initials: H
authors.lastname: Kalimo
authors.forename: J O
authors.initials: JO
authors.lastname: Rinne
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000814:Aniline Compounds; D052160:Benzothiazoles; D001931:Brain Mapping / Q000379:methods; D002250:Carbon Radioisotopes; D002421:Caudate Nucleus / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography / Q000379:methods; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D052160:Benzothiazoles; D002250:Carbon Radioisotopes; D013844:Thiazoles