TY - CHAP
T1 - Noninvasive detection of misfolded proteins in the brain using [11C]BF-227 PET
AU - Okamura, Nobuyuki
AU - Furukawa, Katsutoshi
AU - Furumoto, Shozo
AU - Arai, Hiroyuki
AU - Tashiro, Manabu
AU - Kudo, Yukitsuka
AU - Yanai, Kazuhiko
N1 - Publisher Copyright:
© 2013, IGI Global.
PY - 2013/3/31
Y1 - 2013/3/31
N2 - Alzheimer's disease (AD) and many other neurodegenerative disorders belong to the family of protein misfolding diseases. These diseases are characterized by the deposition of insoluble protein aggregates containing an enriched β-sheet structure. To evaluate PET amyloid-imaging tracer [11C]BF-227 as an agent for in vivo detection of various kinds of misfolded protein, a [11C]BF-227 PET study was performed in patients with various protein misfolding diseases, including AD, frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), sporadic Creutzfeldt-Jakob disease (sCJD) and Gerstmann-Sträussler-Scheinker disease (GSS). BF-227 binds to β-amyloid fibrils with high affinity. Most of the AD patients showed prominent retention of [11C]BF-227 in the neocortex. In addition, neocortical retention of BF-227 was observed in the subjects with mild cognitive impairment who converted to AD during follow-up. DLB patients had elevated [11C]BF-227 uptake in the neocortex. However, FTD and sCJD patients showed no cortical retention of [11C]BF-227. Patients with multiple system atrophy had elevated BF-227 binding in the putamen. Finally, GSS patients had elevated BF-227 uptake in the cerebellum and other brain regions. This chapter confirms that BF-227 can selectively bind to α-synuclein and prion protein deposits using postmortem brain samples. Based on these findings, [11C]BF-227 is not necessarily specific for β-amyloid in AD patients. However, this tracer could be used to detect various types of protein aggregates in the brain.
AB - Alzheimer's disease (AD) and many other neurodegenerative disorders belong to the family of protein misfolding diseases. These diseases are characterized by the deposition of insoluble protein aggregates containing an enriched β-sheet structure. To evaluate PET amyloid-imaging tracer [11C]BF-227 as an agent for in vivo detection of various kinds of misfolded protein, a [11C]BF-227 PET study was performed in patients with various protein misfolding diseases, including AD, frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), sporadic Creutzfeldt-Jakob disease (sCJD) and Gerstmann-Sträussler-Scheinker disease (GSS). BF-227 binds to β-amyloid fibrils with high affinity. Most of the AD patients showed prominent retention of [11C]BF-227 in the neocortex. In addition, neocortical retention of BF-227 was observed in the subjects with mild cognitive impairment who converted to AD during follow-up. DLB patients had elevated [11C]BF-227 uptake in the neocortex. However, FTD and sCJD patients showed no cortical retention of [11C]BF-227. Patients with multiple system atrophy had elevated BF-227 binding in the putamen. Finally, GSS patients had elevated BF-227 uptake in the cerebellum and other brain regions. This chapter confirms that BF-227 can selectively bind to α-synuclein and prion protein deposits using postmortem brain samples. Based on these findings, [11C]BF-227 is not necessarily specific for β-amyloid in AD patients. However, this tracer could be used to detect various types of protein aggregates in the brain.
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U2 - 10.4018/978-1-4666-3604-0.ch025
DO - 10.4018/978-1-4666-3604-0.ch025
M3 - Chapter
AN - SCOPUS:84944035600
SN - 1466636041
SN - 9781466636040
VL - 1
SP - 438
EP - 445
BT - Bioinformatics
PB - IGI Global
ER -