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Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China The pathogenesis of Alzheimer s disease is complex, and early-onset Alzheimer s disease (EOAD) is mostly influenced by genetic factors. Presenilin-1, presenilin-2 (PSEN2), and amyloid precursor protein are currently known as the three main causative genes for autosomal dominant EOAD, with the PSEN2 mutation being the rarest. In this study, we reported a 56-year-old Chinese Han proband who presented with prominent progressive amnesia, aphasia, executive function impairment, and depression 5 years ago. The 3-year follow-up showed that the patient experienced progressive brain atrophy displayed on magnetic resonance imaging (MRI) and dramatic cognitive decline assessed by neuropsychological evaluation. This patient was clinically diagnosed as EOAD based on established criteria. A heterozygous variant (NM 000447.2: c.1106T>C) of PSEN2 was identified for the first time in this patient and her

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