Nonfamilial early-onset Alzheimer's disease associated with de novo PSEN1 mutation: A case report and review of the literature

Abstract

Background Alzheimer's disease (AD) is the most common cognitive disorder, and onset before the age of 65 is defined as early-onset AD (EOAD), accompanied with nonfamilial presenilin 1 (PSEN1) mutation rarely reported. KCNQ2 is a transmembrane potassium channel gene is responsible for epilepsy, the relationship between KCNQ2 mutation and AD with epilepsy is not clear, and there are no reports on the phenotype of KCNQ2 mutation in EOAD. Case presentation we reported a 38-year-old male patient who lacks a family history of AD, presenting with cognitive impairment and seizure at the early stage of disease. After excluding other neurological disorders via a series of comprehensive examinations, including neuropsychological assessment, genetic test, cerebrospinal fluid measurements, 18F-fluorodeoxy glucose-positron emission tomography (PET), 11C-Pittsburgh compound B-PET and 18F-flortaucipir-PET/CT, etc., the patient was finally diagnosed as EOAD with a de novo c.617G > A, (p.Gly206Asp) PSEN1 mutation combined with c.1490G > A (p.Arg497His) potassium voltage-gated channel subfamily Q member 2 (KCNQ2) mutation by AD biomarkers measurements and whole exome sequencing, with different clinical characteristics from previously reported PSEN1 G206D mutation. Conclusions Our case emphasizes the need to consider neurodegenerative diseases in young patients manifesting early cognitive impairment and seizure but lacking a family history of AD, and biomarkers and genes of AD should be tested to make diagnosis. Medication by targeting the brain-gut axis but without the risk of causing seizure is optimal for attenuating cognitive symptoms. KCNQ2 mutation and its role in the development and clinical phenotype of AD needs further exploration.