Heavy Tau Burden with Subtle Amyloid β Accumulation in the Cerebral Cortex and Cerebellum in a Case of Familial Alzheimer’s Disease with APP Osaka Mutation
We previously identified a novel mutation in amyloid precursor protein from a Japanese pedigree of familial Alzheimer’s disease, FAD (Osaka). Our previous positron emission tomography (PET) study revealed that amyloid β (Aβ) accumulation was negligible in two sister cases of this pedigree, indicatin...
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2020-06-01
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| Series: | International Journal of Molecular Sciences |
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| author | Hiroyuki Shimada Shinobu Minatani Jun Takeuchi Akitoshi Takeda Joji Kawabe Yasuhiro Wada Aya Mawatari Yasuyoshi Watanabe Hitoshi Shimada Makoto Higuchi Tetsuya Suhara Takami Tomiyama Yoshiaki Itoh |
| author_facet | Hiroyuki Shimada Shinobu Minatani Jun Takeuchi Akitoshi Takeda Joji Kawabe Yasuhiro Wada Aya Mawatari Yasuyoshi Watanabe Hitoshi Shimada Makoto Higuchi Tetsuya Suhara Takami Tomiyama Yoshiaki Itoh |
| author_sort | Hiroyuki Shimada |
| collection | DOAJ |
| description | We previously identified a novel mutation in amyloid precursor protein from a Japanese pedigree of familial Alzheimer’s disease, FAD (Osaka). Our previous positron emission tomography (PET) study revealed that amyloid β (Aβ) accumulation was negligible in two sister cases of this pedigree, indicating a possibility that this mutation induces dementia without forming senile plaques. To further explore the relationship between Aβ, tau and neurodegeneration, we performed tau and Aβ PET imaging in the proband of FAD (Osaka) and in patients with sporadic Alzheimer’s disease (SAD) and healthy controls (HCs). The FAD (Osaka) patient showed higher uptake of tau PET tracer in the frontal, lateral temporal, and parietal cortices, posterior cingulate gyrus and precuneus than the HCs (>2.5 SD) and in the lateral temporal and parietal cortices than the SAD patients (>2 SD). Most noticeably, heavy tau tracer accumulation in the cerebellum was found only in the FAD (Osaka) patient. Scatter plot analysis of the two tracers revealed that FAD (Osaka) exhibits a distinguishing pattern with a heavy tau burden and subtle Aβ accumulation in the cerebral cortex and cerebellum. These observations support our hypothesis that Aβ can induce tau accumulation and neuronal degeneration without forming senile plaques. |
| first_indexed | 2024-03-10T18:57:33Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:57:33Z |
| publishDate | 2020-06-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b3e497b11c6c4735a1e33ed97a4bc24f2023-11-20T04:38:31ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-012112444310.3390/ijms21124443Heavy Tau Burden with Subtle Amyloid β Accumulation in the Cerebral Cortex and Cerebellum in a Case of Familial Alzheimer’s Disease with APP Osaka MutationHiroyuki Shimada0Shinobu Minatani1Jun Takeuchi2Akitoshi Takeda3Joji Kawabe4Yasuhiro Wada5Aya Mawatari6Yasuyoshi Watanabe7Hitoshi Shimada8Makoto Higuchi9Tetsuya Suhara10Takami Tomiyama11Yoshiaki Itoh12Department of Radiology, Osaka City University Graduate School of Medicine, Osaka 545-8585, JapanDepartment of Neurology, Osaka City University Graduate School of Medicine, Osaka 545-8585, JapanDepartment of Neurology, Osaka City University Graduate School of Medicine, Osaka 545-8585, JapanDepartment of Neurology, Osaka City University Graduate School of Medicine, Osaka 545-8585, JapanDepartment of Nuclear Medicine, Osaka City University Graduate School of Medicine, Osaka 545-8585, JapanRIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, JapanRIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, JapanRIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, JapanDepartment of Functional Brain Imaging Research (DOFI), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba 263-8555, JapanDepartment of Functional Brain Imaging Research (DOFI), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba 263-8555, JapanDepartment of Functional Brain Imaging Research (DOFI), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba 263-8555, JapanDepartment of Translational Neuroscience, Osaka City University Graduate School of Medicine, Osaka 545-8585, JapanDepartment of Neurology, Osaka City University Graduate School of Medicine, Osaka 545-8585, JapanWe previously identified a novel mutation in amyloid precursor protein from a Japanese pedigree of familial Alzheimer’s disease, FAD (Osaka). Our previous positron emission tomography (PET) study revealed that amyloid β (Aβ) accumulation was negligible in two sister cases of this pedigree, indicating a possibility that this mutation induces dementia without forming senile plaques. To further explore the relationship between Aβ, tau and neurodegeneration, we performed tau and Aβ PET imaging in the proband of FAD (Osaka) and in patients with sporadic Alzheimer’s disease (SAD) and healthy controls (HCs). The FAD (Osaka) patient showed higher uptake of tau PET tracer in the frontal, lateral temporal, and parietal cortices, posterior cingulate gyrus and precuneus than the HCs (>2.5 SD) and in the lateral temporal and parietal cortices than the SAD patients (>2 SD). Most noticeably, heavy tau tracer accumulation in the cerebellum was found only in the FAD (Osaka) patient. Scatter plot analysis of the two tracers revealed that FAD (Osaka) exhibits a distinguishing pattern with a heavy tau burden and subtle Aβ accumulation in the cerebral cortex and cerebellum. These observations support our hypothesis that Aβ can induce tau accumulation and neuronal degeneration without forming senile plaques.https://www.mdpi.com/1422-0067/21/12/4443amyloid PETtau PETamyloid precursor proteinmutationfamilial Alzheimer’s diseasecerebellum |
| spellingShingle | Hiroyuki Shimada Shinobu Minatani Jun Takeuchi Akitoshi Takeda Joji Kawabe Yasuhiro Wada Aya Mawatari Yasuyoshi Watanabe Hitoshi Shimada Makoto Higuchi Tetsuya Suhara Takami Tomiyama Yoshiaki Itoh Heavy Tau Burden with Subtle Amyloid β Accumulation in the Cerebral Cortex and Cerebellum in a Case of Familial Alzheimer’s Disease with APP Osaka Mutation International Journal of Molecular Sciences amyloid PET tau PET amyloid precursor protein mutation familial Alzheimer’s disease cerebellum |
| title | Heavy Tau Burden with Subtle Amyloid β Accumulation in the Cerebral Cortex and Cerebellum in a Case of Familial Alzheimer’s Disease with APP Osaka Mutation |
| title_full | Heavy Tau Burden with Subtle Amyloid β Accumulation in the Cerebral Cortex and Cerebellum in a Case of Familial Alzheimer’s Disease with APP Osaka Mutation |
| title_fullStr | Heavy Tau Burden with Subtle Amyloid β Accumulation in the Cerebral Cortex and Cerebellum in a Case of Familial Alzheimer’s Disease with APP Osaka Mutation |
| title_full_unstemmed | Heavy Tau Burden with Subtle Amyloid β Accumulation in the Cerebral Cortex and Cerebellum in a Case of Familial Alzheimer’s Disease with APP Osaka Mutation |
| title_short | Heavy Tau Burden with Subtle Amyloid β Accumulation in the Cerebral Cortex and Cerebellum in a Case of Familial Alzheimer’s Disease with APP Osaka Mutation |
| title_sort | heavy tau burden with subtle amyloid β accumulation in the cerebral cortex and cerebellum in a case of familial alzheimer s disease with app osaka mutation |
| topic | amyloid PET tau PET amyloid precursor protein mutation familial Alzheimer’s disease cerebellum |
| url | https://www.mdpi.com/1422-0067/21/12/4443 |
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