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

Tetsuya Suhara¹  Hitoshi Shimada¹  Makoto Higuchi¹  Shinobu Minatani²  Jun Takeuchi²  Akitoshi Takeda²  Yoshiaki Itoh²  Joji Kawabe³  Hiroyuki Shimada⁴  Takami Tomiyama⁵  Yasuhiro Wada⁶  Aya Mawatari⁶  Yasuyoshi Watanabe⁶ 

[1] Department of Functional Brain Imaging Research (DOFI), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba 263-8555, Japan;Department of Neurology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan;Department of Nuclear Medicine, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan;Department of Radiology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan;Department of Translational Neuroscience, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan;RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan;

关键词: amyloid PET;    tau PET;    amyloid precursor protein;    mutation;    familial Alzheimer’s disease;    cerebellum;   

DOI  :  10.3390/ijms21124443

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown