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Positron emission tomography imaging and clinical progression in relation to molecular pathology in the first Pittsburgh Compound B positron emission tomography patient with Alzheimer’s disease
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2011 (English)In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 134, no 1, 301-317 p.Article in journal (Refereed) Published
Abstract [en]

The accumulation of β-amyloid in the brain is an early event in Alzheimer’s disease. This study presents the first patient with Alzheimer’s disease who underwent positron emission tomography imaging with the amyloid tracer, Pittsburgh Compound B to visualize fibrillar β-amyloid in the brain. Here we relate the clinical progression, amyloid and functional brain positron emission tomography imaging with molecular neuropathological alterations at autopsy to gain new insight into the relationship between β-amyloid accumulation, inflammatory processes and the cholinergic neurotransmitter system in Alzheimer’s disease brain. The patient underwent positron emission tomography studies with 18F-fluorodeoxyglucose three times (at ages 53, 56 and 58 years) and twice with Pittsburgh Compound B (at ages 56 and 58 years), prior to death at 61 years of age. The patient showed a pronounced decline in cerebral glucose metabolism and cognition during disease progression, while Pittsburgh Compound B retention remained high and stable at follow-up. Neuropathological examination of the brain at autopsy confirmed the clinical diagnosis of pure Alzheimer’s disease. A comprehensive neuropathological investigation was performed in nine brain regions to measure the regional distribution of β-amyloid, neurofibrillary tangles and the levels of binding of 3H-nicotine and 125I-α-bungarotoxin to neuronal nicotinic acetylcholine receptor subtypes, 3H-L-deprenyl to activated astrocytes and 3H-PK11195 to microglia, as well as butyrylcholinesterase activity. Regional in vivo 11C-Pittsburgh Compound B-positron emission tomography retention positively correlated with 3H-Pittsburgh Compound B binding, total insoluble β-amyloid, and β-amyloid plaque distribution, but not with the number of neurofibrillary tangles measured at autopsy. There was a negative correlation between regional fibrillar β-amyloid and levels of 3H-nicotine binding. In addition, a positive correlation was found between regional 11C-Pittsburgh Compound B positron emission tomography retention and 3H-Pittsburgh Compound B binding with the number of glial fibrillary acidic protein immunoreactive cells, but not with 3H-L-deprenyl and 3H-PK-11195 binding. In summary, high 11C-Pittsburgh Compound B positron emission tomography retention significantly correlates with both fibrillar β-amyloid and losses of neuronal nicotinic acetylcholine receptor subtypes at autopsy, suggesting a closer involvement of β-amyloid pathology with neuronal nicotinic acetylcholine receptor subtypes than with inflammatory processes.

Place, publisher, year, edition, pages
2011. Vol. 134, no 1, 301-317 p.
Keyword [en]
Alzheimer’s disease, autopsy brain, 11C-PIB positron emission tomography, inflammation, nicotinic acetylcholine receptors
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Research subject
URN: urn:nbn:se:su:diva-55638DOI: 10.1093/brain/awq349OAI: diva2:405762
The authors thank Dr Lena Cavallin (Department of Radiology, Karolinska University Hospital Huddinge, Stockholm) for evaluation of the MRI scan and Dr Anders Wall (Uppsala PET Centre/Uppsala Imanet AB) for his assistance with preparing PET figures. We also express our sincere gratitude to the patient and her relatives for participation and permission to accomplish this study. Finally, we will dedicate this study to the memory of the patient.Available from: 2011-03-23 Created: 2011-03-23 Last updated: 2011-04-15Bibliographically approved

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Almkvist, Ove
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Department of Psychology
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