Presenilin 1 gene mutations: a potential marker to help diagnose early onset Alzheimer’s disease

Abstract

Alzheimer’s disease is a prevalent neurodegenerative disorder that affects millions of people worldwide with a substantial healthcare expenditure of almost $500 billion dollars. Alzheimer’s is primarily considered a disease of the aging population, with 95% of cases being diagnosed in patients over 65. Alzheimer’s in patients under 65 years of age are termed early onset Alzheimer’s disease (EOAD). The clinical presentation and disease mechanism of EOAD are quite distinct from typical Alzheimer’s. For example, EOAD patients often experience more rapid cognitive decline and have cortical region atrophy as opposed to temporal region atrophy. The atypical nature of EOAD frequently leads to delayed diagnosis and treatment. This delay is especially problematic for EOAD patients because they are at a stage of life with significant responsibilities such as maintaining their careers and families. This case study examines a previously healthy 32-year-old man that was mistakenly suspected of having frontotemporal dementia. Alzheimer’s was not considered as a correct diagnosis due to the atypical symptoms and weak family history for the disease. For these reasons, genetic analysis was not used to help make a diagnosis. The patient died at the age of 36 and autopsy revealed markers of Alzheimer’s including neuritic plaques and tau neurofibrillary tangles. Genetic analysis revealed no presenilin 1 (PSEN1) mutations which has been associated with EOAD. However, this patient may have had deletion mutations that could not be investigated due to the lack of frozen tissue for RNA analysis. This case illustrates the importance of genetic testing for EOAD diagnosis.