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SORL1 Variants in Familial Alzheimer's Disease.
Estrella Gómez-Tortosa1, María Ruggiero1, Ma José Sainz1
1Department of Neurology, Fundación Jiménez Díaz, Madrid, Spain.
Journal of Alzheimer'S Disease : JAD
|January 30, 2018
Summary
Genetic variants in the SORL1 gene were investigated in familial Alzheimer's disease (AD). While SORL1 mutations were found in 7% of cases, most were not directly linked to the disease, with two variants remaining likely correlated.
Area of Science:
- Genetics
- Neuroscience
- Molecular Biology
Background:
- The SORL1 gene plays a role in the amyloidogenic pathway.
- Variants in SORL1 have been implicated in Alzheimer's disease (AD) pathophysiology.
- Familial dementia of Alzheimer type (DAT) presents a valuable cohort for genetic studies.
Purpose of the Study:
- To screen for SORL1 gene variants in familial dementia of Alzheimer type (DAT) cases.
- To assess the potential causal relationship between identified SORL1 variants and AD.
- To determine the frequency and significance of SORL1 mutations in familial AD.
Main Methods:
- Screening of 124 familial DAT cases (early- and late-onset) for SORL1 variants.
- Identification of potentially pathogenic changes, including novel and rare variants.
- Segregation analysis in control populations and siblings to evaluate variant causality.
Main Results:
- Nine potentially pathogenic SORL1 variants were identified in 7% of familial DAT probands.
- Six variants were deemed unlikely to be causally related to AD after control and segregation analysis.
- Two variants, Trp848Ter and a splice-site variant, remained likely correlated with the disease.
Conclusions:
- SORL1 mutations are present in a subset of familial DAT patients.
- In most instances, identified SORL1 variants are not the direct cause of familial AD.
- Specific SORL1 variants, including Trp848Ter, warrant further investigation for their role in AD pathogenesis.