Case of Autosomal Dominant Alzheimer Disease With Negative Findings From PiB-PET Examination.

Background and Objectives: This study reports an uncommon case of autosomal dominant Alzheimer disease (AD) with negative PiB-PET findings. Methods: A 55-year-old woman was admitted to the hospital due to a progressive cognitive decline for over 9 years, along with a possible dementia family history. The patient underwent routine laboratory tests, neuropsychological assessments, and neuroimaging examinations. Additionally, the cerebrospinal fluid sample was analyzed for AD biomarkers using the Single Molecular Array (Simoa) technique. A targeted Next-Generation-Sequencing (NGS) panel screening was also conducted. Results: Routine blood and CSF laboratory tests, as well as CSF tap test, yielded negative results. Cranial MRI showed atrophy of the whole brain. PiB-PET scanning indicated that PiB was merely retained in her brain with an overall standard uptake value ratio (SUVR) <1.0. Simoa analysis showed an increase in the level of CSF t-tau and a decrease in that of CSF Aβ42. NGS panel screening detected a c.G2032A (p.D678N) heterozygous mutation in APP. Consequently, the patient was diagnosed with autosomal dominant AD. Discussion: We have reported an uncommon case of autosomal dominant AD carrying p.D678N variant in APP with negative PiB-PET results. The diagnosis of AD should not be directly excluded solely based on the negative PiB-PET results.