title: Early-onset Alzheimers and cortical vision impairment in a woman with valosin-containing protein disease associated with 2 APOE ε4/APOE ε4 genotype.
abstract: Hereditary inclusion body myopathy is a heterogeneous group of disorders characterized by rimmed vacuoles and by the presence of filamentous cytoplasmic and intranuclear inclusions. Inclusion body myopathy with Paget disease of bone and frontotemporal dementia is a progressive autosomal dominant disorder associated with a mutation in valosin-containing protein (VCP) with typical onset of symptoms in the 30s. APOE [Latin Small Letter Open E]4 is a major risk factor for late-onset Alzheimer disease, a progressive neurodegenerative disorder that affects memory, thinking, behavior, and emotion as a result of the excessive buildup and decreased clearance of β-amyloid proteins resulting in the appearance of neuritic plaques and neurofibrillary tangles. In conclusion, we report a unique patient with an APOE [Latin Small Letter Open E]4/APOE [Latin Small Letter Open E]4 genotype and atypical VCP disease associated with early Alzheimer disease and severe vision impairment. Future studies will elucidate the interaction of VCP mutations and APOE [Latin Small Letter Open E]4 alleles in understanding common mechanisms in AD and VCP disease.
authors.affiliation: *Department of Pediatrics, Division of Genetics and Metabolism, University of California, Irvine ‡Department of Pathology, University of California Medical Center, Orange, CA †Department of Pathology, University of Maryland School of Medicine, Baltimore, MD.
authors.forename: Sharis
authors.initials: S
authors.lastname: Shamirian
authors.forename: Angèle
authors.initials: A
authors.lastname: Nalbandian
authors.forename: Manaswitha
authors.initials: M
authors.lastname: Khare
authors.forename: Rudolph
authors.initials: R
authors.lastname: Castellani
authors.forename: Ronald
authors.initials: R
authors.lastname: Kim
authors.forename: Virginia E
authors.initials: VE
authors.lastname: Kimonis
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000544:Alzheimer Disease / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D001766:Blindness / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D000074405:Valosin Containing Protein
chemical_list: D053327:Apolipoprotein E4; D018797:Cell Cycle Proteins; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein