[11C]PIB binding in Parkinson's disease dementia.
[(11)C]PIB ((11)C-6-OH benzothiazole) reflects the regional distribution of amyloid (beta-sheeted proteins) in patients with Alzheimer's disease (AD). Proteinaceous inclusions in Parkinson's disease with dementia (PDD), so-called Lewy bodies, also consist of fibrillar, misfolded proteins, chiefly alpha-synuclein. To test whether PDD subjects show specific amyloid binding in vivo and whether this could reflect fibrillar alpha-synuclein accumulation, we investigated 10 PDD subjects with [(11)C]PIB-PET. Radioligand binding was compared to that in 11 control and 6 AD subjects. Furthermore, postmortem sections of 4 patients with Parkinson's disease (PD), therefrom 2 with dementia (PDD), and of 6 controls were stained with PIB to evaluate the histological distribution of the fluorescent ligand in the brainstem. In PET, only 2 PDD patients displayed increased PIB binding to cortical amyloid comparable to AD patients. The other 8 patients showed control-like cortical findings but elevated PIB binding in the pons and mesencephalon. Fluorescence microscopy showed PIB binding to Lewy bodies and neuromelanin in the substantia nigra of PD and PDD brainstem sections, but not in controls. These data suggest that PIB-PET can be used to further differentiate PDD with respect to cortical amyloid. Furthermore, we provide evidence that--in addition to nonspecific binding--PIB uptake in the brainstem may also reflect PDD related amyloid.
Hertie Institute for Clinical Brain Research, Department of Neurodegenerative Diseases, University of Tuebingen, Tuebingen, Germany.
Walter
W
Maetzler
Matthias
M
Reimold
Inga
I
Liepelt
Christoph
C
Solbach
Thomas
T
Leyhe
Katherine
K
Schweitzer
Gerhard W
GW
Eschweiler
Michel
M
Mittelbronn
Alexandra
A
Gaenslen
Michael
M
Uebele
Gerald
G
Reischl
Thomas
T
Gasser
Hans-Jürgen
HJ
Machulla
Roland
R
Bares
Daniela
D
Berg
D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000814:Aniline Compounds; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D003704:Dementia / Q000000981:diagnostic imaging* / Q000209:etiology*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000000981:diagnostic imaging; D008297:Male; D008543:Melanins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications* / Q000000981:diagnostic imaging*; D017433:Protein Structure, Secondary; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D013844:Thiazoles
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D008543:Melanins; D019275:Radiopharmaceuticals; D013844:Thiazoles; C014121:neuromelanin