Heavy Tau Burden with Subtle Amyloid beta 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 beta (A beta) 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 A beta, tau and neurodegeneration, we performed tau and A beta 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 A beta accumulation in the cerebral cortex and cerebellum. These observations support our hypothesis that A beta can induce tau accumulation and neuronal degeneration without forming senile plaques.