APP 3’UTR VARIANT IN A PATIENT WITH MCI AND WITHOUT SIGNS OF CEREBRAL AMYLOID ANGIOPATHY: A CASE REPORT

Abstract

Familial Alzheimer's disease (FAD) is associated with mutations in the amyloid precursor protein gene (APP). Recent studies discussed possible relations between cerebral amyloid angiopathy (CAA) and APP variants or duplications (Nicolas G et al. Mutation in the 3'untranslated region of APP as a genetic determinant of cerebral amyloid angiopathy. European Journal of Human Genetics 2016; 24: 92–98). Nicolas et al. identified APP 3'UTR (3'untranslated region of APP) sequence variants including c.*18C>T as possible genetic determinants of CAA. This is the case of a 51-year-old female patient with an APP 3'UTR sequence variant, admitted to the clinic due to depressive symptoms. After full remission of the severe depressive episode (ICD-10), the patient still suffered from cognitive impairment. Brain MRI-scan revealed frontal lobe atrophy. Electroencephalogram was normal. Neuropsychological assessments showed moderate impairment in tasks on recall of nonverbal visuospatial information as well as in the ability to learn new task rules and slight impairment in tasks on delayed recall of verbal information. 18FDG-positron-emission-tomography and cerebrospinal fluid analysis including beta-amyloid and tau-protein were unremarkable. Due to these conflicting findings and to the patient's relatively young age, genetic DNA analysis was conducted. Genetic DNA analysis led to detection of the heterozygous APP 3'UTR sequence variant c.*18C>T, so far of unknown significance and with a minor allele frequency of less than 0.01 %. No radiological signs of cerebral amyloid angiopathy were found in this patient. She had no family history of psychiatric diseases and was currently diagnosed with mild cognitive impairment, not meeting the criteria for dementia (yet). Thorough follow-up examinations including frequent evaluations of vascular risk factors are necessary to detect early signs of CAA in this patient and to reduce her risk of brain hemorrhage. The reported APP 3'UTR sequence variant could be a genetic determinant of the development of cognitive impairment, possibly of Alzheimer's disease. Further research and longitudinal studies are necessary to test this hypothesis and to also examine if this variant is a genetic determinant of CAA.