Affiliations: [a] Department of Neurology, Fundación Jiménez Díaz, Madrid, Spain
| [b] Department of Neurology, Hospital 12 Octubre, Madrid, Spain
| [c] Department of Neurology, Hospital Infanta Elena, Madrid, Spain
| [d] Instituto de Investigaciones Sanitarias Fundación Jiménez Díaz (IIS-FJD) and CIBERER (Madrid), Madrid, Spain
| [e] Secugen S.L. Madrid, Spain
Correspondence:
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Correspondence to: Estrella Gómez-Tortosa, MD, PhD, Department of Neurology, Fundación Jiménez Díaz, Avenida de los Reyes Católicos 2, 28040 Madrid, Spain. Tel.: +34 91 5504800; Ext. 2063; E-mail: egomezt@fjd.es.
Abstract: The SORL1 gene encodes a protein involved in the amyloidogenic process, and its variants have been associated with Alzheimer’s disease (AD) physiopathology. We screened for SORL1 variants in 124 familial (44 early- and 80 late-onset) dementia of Alzheimer type (DAT) cases. Nine potentially pathogenic changes (three not previously reported and six rare variants) were found in nine probands (7%). After screening the control population and siblings (presence in at least 1/200 controls and/or absence of segregation pattern), a causal relationship with the disease was considered unlikely in six variants and uncertain in one. The change Trp848Ter and a splice-site variant remained likely correlated with the disease. SORL1 mutations are present in 7% of our familial DAT cohort, though in most cases cannot be considered the direct cause of the disease.
Keywords: Alzheimer’s disease, familial, neurogenetics, SORL1 gene, SORLA protein
