Related Experiment Video
Updated: Jun 13, 2026
Hybrid PET/MRI Imaging of Alzheimer's Disease Based on 18F-AV-1451
Published on: April 18, 2025
In vivo detection of neuropathologic changes in presymptomatic MAPT mutation carriers: a PET and MRI study
Michie Miyoshi1, Hitoshi Shinotoh, Zbigniew K Wszolek
1Molecular Neuroimaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba, Japan.
Background:
Microglial activation and disrupted neurotransmissions may herald symptomatic manifestations in neurodegenerative tauopathies.
Methods:
We investigated microglial activation with [(11)C]DAA1106 positron emission tomography (PET), striatal dopaminergic function with l-[beta-(11)C]dopa PET, acetylcholinesterase (AChE) activity with [(11)C]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 [(11)C]DAA1106 PET results from age-matched 9 healthy volunteers (HV), and with l-[beta-(11)C]dopa and [(11)C]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.
Insights
Presymptomatic carriers of FTDP-17 gene mutations show early signs of brain changes, including hippocampal atrophy and reduced dopamine function, suggesting these may precede overt symptoms in this neurodegenerative disease.
Area of Science:
- Neuroscience
- Neurology
- Radiology
Background:
- Neurodegenerative tauopathies are associated with microglial activation and neurotransmission disruption.
- These changes may precede the symptomatic onset of neurodegenerative diseases.
Purpose of the Study:
- To investigate early neuroimaging markers in presymptomatic carriers of the FTDP-17 gene mutation.
- To correlate glial activation, dopaminergic function, acetylcholinesterase activity, and brain morphology in individuals at risk for FTDP-17.
Main Methods:
- Utilized positron emission tomography (PET) with tracers for microglial activation ([ (11)C]DAA1106), dopaminergic function (l-[beta-(11)C]dopa), and acetylcholinesterase (AChE) activity ([(11)C]N-methylpiperidin-4-yl acetate).
- Assessed morphologic brain changes using magnetic resonance imaging (MRI).
- Compared findings in three presymptomatic gene carriers (PGCs) with healthy volunteers (HV).
Main Results:
- Increased glial activity was observed in various cortical regions in PGCs, though not overtly.
- Reduced AChE activity was noted in the temporo-parietal cortex in one PGC.
- Striatal dopaminergic dysfunction and hippocampal atrophy were present in PGCs, with three showing low dopamine synthesis rates and two exhibiting hippocampal atrophy.
Conclusions:
- Hippocampal atrophy and striatal dopaminergic dysfunction are potential early indicators in the pathogenesis of FTDP-17.
- Neuroinflammation may serve as an in vivo signature of tau pathology at a prodromal stage.
- Current PET techniques may not consistently detect neuroinflammation as the earliest neuroimaging abnormality.
