Skip to Main content Skip to Navigation
Journal articles

APP Mutations in Cerebral Amyloid Angiopathy with or without Cortical Calcifications: Report of Three Families and a Literature Review

Abstract : BACKGROUND: Specific APP mutations cause cerebral amyloid angiopathy (CAA) with or without Alzheimer's disease (AD). OBJECTIVE: We aimed at reporting APP mutations associated with CAA, describe the clinical, cerebrospinal fluid AD biomarkers, and neuroimaging features, and compare them with the data from the literature. METHODS: We performed a retrospective study in two French genetics laboratories by gathering all clinical and neuroimaging data from patients referred for a genetic diagnosis of CAA with an age of onset before 66 years and fulfilling the other Boston revised criteria. We studied the segregation of mutations in families and performed a comprehensive literature review of all cases reported with the same APP mutation. RESULTS: We screened APP in 61 unrelated French patients. Three mutations, located in the Aβ coding region, were detected in five patients from three families: p.Ala692Gly (Flemish), p.Glu693Lys (Italian), and p.Asp694Asn (Iowa). Patients exhibited CAA and progressive cognitive impairment associated with cortical calcifications in the Iowa and Italian mutation carriers, but not the patient carrying the Flemish mutation. CONCLUSIONS: This is the first evidence of cortical calcification in patients with an APP mutation other than the Iowa mutation. We discuss the radiological, cerebrospinal fluid, and clinical phenotype of patients carrying these mutations in the literature.
Document type :
Journal articles
Complete list of metadatas

https://hal-amu.archives-ouvertes.fr/hal-01425503
Contributor : Monique Bernard <>
Submitted on : Tuesday, January 3, 2017 - 3:55:39 PM
Last modification on : Wednesday, August 19, 2020 - 12:08:19 PM

Identifiers

Citation

François Sellal, David Wallon, Laurent Martinez-Almoyna, Cecilia Marelli, Abhinav Dhar, et al.. APP Mutations in Cerebral Amyloid Angiopathy with or without Cortical Calcifications: Report of Three Families and a Literature Review. Journal of Alzheimer's disease: JAD, 2016, ⟨10.3233/JAD-160709⟩. ⟨hal-01425503⟩

Share

Metrics

Record views

498