Public Health.

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Hereditary Alzheimer's disease (AD) is linked to variants in APP, PSEN1, and PSEN2 genes.
• PSEN2 variants are a rare cause of familial AD.
• Understanding genetic heterogeneity in AD is crucial for diagnosis and treatment.

Purpose of the Study:

• To report the first case of hereditary AD in Japan associated with a PSEN2 variant.
• To characterize the clinical and genetic profile of a patient with a novel PSEN2 variant.
• To contribute to the understanding of rare PSEN2-related AD.

Main Methods:

• Clinical evaluation of a patient with suspected hereditary AD.
• Genetic laboratory analysis including multi-gene sequencing for AD-related genes.
• Neuropsychological and neuroradiological assessments (MRI, amyloid PET).

Main Results:

• A 51-year-old Japanese woman presented with early-onset dementia and a family history of dementia.
• Clinical and imaging findings were consistent with AD.
• Novel heterozygous missense variants in PSEN2 (c.356T>G, p.Leu119Arg) were identified.
• Lecanemab treatment was initiated at age 50.

Conclusions:

• This is the first reported hereditary AD patient with a PSEN2 variant in Japan.
• The study highlights the importance of genetic testing for rare PSEN2 variants in AD.
• Further research on the clinical and genetic characteristics of novel PSEN2 variants is warranted.