Early-onset Alzheimer’s disease patient with prion (PRNP) p.Val180Ile mutation

Eva Bagyinszky1,*, Min Ju Kang2,*, Jungmin Pyun,3 Vo Van Giau,1 Seong Soo A An,1 SangYun Kim31Department of Bionano Technology, Gachon Medical Research Institute, Gachon University, Sungnamsi 461-701, Republic of Korea; 2Department of Neurology, Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul, Republic of Korea; 3Department of Neurology, Seoul National University College of Medicine and Neurocognitive Behavior Center, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, 463-707, Republic of Korea*These authors contributed equally to this workBackground: In this study, a known PRNP mutation, Val180Ile (c.G538A), was reported in a 58 years old female patient, clinically diagnosed with Alzheimer’s disease (AD).Case report: The patient presented slowly progressive cognitive decline in memory and visuospatial domain. Neuroimaging showed hippocampal atrophy in MRI and mild amyloid positivity in PET scan. Even though her cerebrospinal fluid (CSF) was positive for 14–3-3 protein, no sign of Creutzfeldt-Jakob diseases symptoms was observed. In addition, reduced Aβ42 and elevated total-Tau and phospho-Tau in CSF also proved the AD diagnosis. The mutation may disturb the hydrophobic core of prion protein, and result in abnormal intramolecular interactions. Due to 23andMe, PRNP Val180Ile could not be categorized either as a mutation with complete penetrance, or as neutral variant, and could have a possible role in neurodegeneration. Pathological overlap was observed between prion diseases and other neurodegenerative diseases, including AD or frontotemporal dementia.Conclusion: Whole exome sequencing and pathway analysis of patient revealed rare or possible risk variants in AD associated genes, such as SORL1 or ABCA7. Along with PRNP, AD risk genes may play a role in negative regulation of amyloid formation. Dysfunctions in these genes could possibly be associated in reduced neuroprotection and amyloid clearance.Keywords: Alzheimer’s disease, prion, PRNP Val180Ile mutation, Creutzfelt -Jakob disease