Affiliations: Regional Neurogenetic Centre, ASP Catanzaro, Lamezia Terme (CZ), Italy
Correspondence:
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Corresponding author: Dr. A.C. Bruni, Centro Regionale di Neurogenetica, Azienda Sanitaria Provinciale Catanzaro, Viale A. Perugini, 88046 Lamezia Terme (CZ), Italy. Tel.: +39 0968 208080; Fax: +39 0968 208032; E-mail: [email protected].
Note: [1] These authors contributed equally to this work.
Note: [] Communicated by Patrizia Mecocci
Abstract: Mutations in the amyloid-β protein precursor (AβPP) gene can cause autosomal dominant early-onset Alzheimer's disease, or Alzheimer's disease (AD) associated with cerebral amyloid angiopathy (CAA), cerebral hemorrhage, or both. We have previously reported that the AβPP A713T mutation is associated with AD and subcortical ischemic lesions at magnetic resonance imaging in a large family which neuropathology confirmed CAA, stroke, and AD lesions. The objective of this clinical and molecular study was to investigate AβPP gene mutations in 59 patients affected by AD with cerebrovascular lesions (CVLs) and a family history of dementia. We identified three affected subjects with the AβPP A713T mutation. Since the prevalence of this mutation worldwide is very low, a common founder could exist in southern Italy. The pathogenicity of this mutation was confirmed and the clinical AD phenotype with CVLs seems to be a distinctive feature in the southern Italian population. The identification of these patients suggests that genetic epidemiology in large cohorts of familial late onset AD with CVLs would increase the probability of identifying AβPP mutations.
