Journal
BRAIN
Volume 134, Issue -, Pages 301-317Publisher
OXFORD UNIV PRESS
DOI: 10.1093/brain/awq349
Keywords
Alzheimer's disease; autopsy brain; C-11-PIB positron emission tomography; inflammation; nicotinic acetylcholine receptors
Categories
Funding
- Swedish Research Council [05817]
- Swedish Brain Power
- Stockholm County Council-Karolinska Institutet
- Karolinska Institutet Strategic Neuroscience Program
- EC [LSHB-CT-2005-512146]
- Swedish Brain Foundation
- Alzheimer Foundation in Sweden
- Magnus Bergvalls Foundation
- Demensfonden
- foundation for Old Servants
- Gun and Bertil Stohnes Foundation
- Karolinska Institutet foundations
- Lars Hierta Memorial Foundation
- Olle Engkvist Byggmastare Foundation
Ask authors/readers for more resources
The accumulation of beta-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 beta-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 beta-amyloid accumulation, inflammatory processes and the cholinergic neurotransmitter system in Alzheimer's disease brain. The patient underwent positron emission tomography studies with F-18-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 beta-amyloid, neurofibrillary tangles and the levels of binding of H-3-nicotine and I-125-alpha-bungarotoxin to neuronal nicotinic acetylcholine receptor subtypes, H-3-L-deprenyl to activated astrocytes and H-3-PK11195 to microglia, as well as butyrylcholinesterase activity. Regional in vivo C-11-Pittsburgh Compound B-positron emission tomography retention positively correlated with H-3-Pittsburgh Compound B binding, total insoluble beta-amyloid, and beta-amyloid plaque distribution, but not with the number of neurofibrillary tangles measured at autopsy. There was a negative correlation between regional fibrillar beta-amyloid and levels of H-3-nicotine binding. In addition, a positive correlation was found between regional C-11-Pittsburgh Compound B positron emission tomography retention and H-3-Pittsburgh Compound B binding with the number of glial fibrillary acidic protein immunoreactive cells, but not with H-3-L-deprenyl and H-3-PK-11195 binding. In summary, high C-11-Pittsburgh Compound B positron emission tomography retention significantly correlates with both fibrillar beta-amyloid and losses of neuronal nicotinic acetylcholine receptor subtypes at autopsy, suggesting a closer involvement of beta-amyloid pathology with neuronal nicotinic acetylcholine receptor subtypes than with inflammatory processes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available