TY - JOUR
T1 - In vivo detection of neuropathologic changes in presymptomatic MAPT mutation carriers
T2 - A PET and MRI study
AU - Miyoshi, Michie
AU - Shinotoh, Hitoshi
AU - Wszolek, Zbigniew K.
AU - Strongosky, Audrey J.
AU - Shimada, Hitoshi
AU - Arakawa, Ryosuke
AU - Higuchi, Makoto
AU - Ikoma, Yoko
AU - Yasuno, Fumihiko
AU - Fukushi, Kiyoshi
AU - Irie, Toshiaki
AU - Ito, Hiroshi
AU - Suhara, Tetsuya
PY - 2010/7
Y1 - 2010/7
N2 - Background: Microglial activation and disrupted neurotransmissions may herald symptomatic manifestations in neurodegenerative tauopathies. Methods: We investigated microglial activation with [11C]DAA1106 positron emission tomography (PET), striatal dopaminergic function with l-[β-11C]dopa PET, acetylcholinesterase (AChE) activity with [11C]N-methylpiperidin-4-yl acetate PET, and morphologic brain changes with MRI in three persons (aged 38-41 years) with frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), who were presymptomatic gene carriers (PGCs) from an American kindred with pallidopontonigral degeneration. The results from these 3 PGCs were compared with [11C]DAA1106 PET results from age-matched 9 healthy volunteers (HV), and with l-[β-11C]dopa and [11C]MP4A PET results from 10 HV. Values considered significant were more than 2 SDs greater or less than the normal control mean, as the number of subjects was small for group comparisons. Results: Glial activities were increased in the frontal cortex of one PGC, the occipital cortex of two PGCs, and the posterior cingulate cortex of one PGC, although none of the PGCs showed overt glial activation in the brain. Only one of the PGCs showed reduced AChE activity in the temporo-parietal cortex. Three PGCs showed low dopamine synthesis rates in the putamen. Hippocampal atrophy was observed in two PGCs. Conclusions: Hippocampal atrophy and striatal dopaminergic dysfunction may be early disease processes in the pathogenesis of FTDP-17. Neuroinflammation may also be an in vivo signature of tau pathology at a prodromal stage, although current PET techniques may not constantly reveal it as the earliest neuroimaging abnormality.
AB - Background: Microglial activation and disrupted neurotransmissions may herald symptomatic manifestations in neurodegenerative tauopathies. Methods: We investigated microglial activation with [11C]DAA1106 positron emission tomography (PET), striatal dopaminergic function with l-[β-11C]dopa PET, acetylcholinesterase (AChE) activity with [11C]N-methylpiperidin-4-yl acetate PET, and morphologic brain changes with MRI in three persons (aged 38-41 years) with frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), who were presymptomatic gene carriers (PGCs) from an American kindred with pallidopontonigral degeneration. The results from these 3 PGCs were compared with [11C]DAA1106 PET results from age-matched 9 healthy volunteers (HV), and with l-[β-11C]dopa and [11C]MP4A PET results from 10 HV. Values considered significant were more than 2 SDs greater or less than the normal control mean, as the number of subjects was small for group comparisons. Results: Glial activities were increased in the frontal cortex of one PGC, the occipital cortex of two PGCs, and the posterior cingulate cortex of one PGC, although none of the PGCs showed overt glial activation in the brain. Only one of the PGCs showed reduced AChE activity in the temporo-parietal cortex. Three PGCs showed low dopamine synthesis rates in the putamen. Hippocampal atrophy was observed in two PGCs. Conclusions: Hippocampal atrophy and striatal dopaminergic dysfunction may be early disease processes in the pathogenesis of FTDP-17. Neuroinflammation may also be an in vivo signature of tau pathology at a prodromal stage, although current PET techniques may not constantly reveal it as the earliest neuroimaging abnormality.
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U2 - 10.1016/j.parkreldis.2010.04.004
DO - 10.1016/j.parkreldis.2010.04.004
M3 - Article
C2 - 20452812
AN - SCOPUS:77953614566
SN - 1353-8020
VL - 16
SP - 404
EP - 408
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
IS - 6
ER -