AbetaPP A713T mutation in late onset Alzheimer's disease with cerebrovascular lesions.
Mutations in the amyloid-beta protein precursor (AbetaPP) 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 AbetaPP 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 AbetaPP 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 AbetaPP 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 AbetaPP mutations.
Bernardi
Livia
L
Regional Neurogenetic Centre, ASP Catanzaro, Lamezia Terme (CZ), Italy.
Geracitano
Silvana
S
Colao
Rosanna
R
Puccio
Gianfranco
G
Gallo
Maura
M
Anfossi
Maria
M
Frangipane
Francesca
F
Curcio
Sabrina A M
SA
Mirabelli
Maria
M
Tomaino
Carmine
C
Vasso
Franca
F
Smirne
Nicoletta
N
Maletta
Raffaele
R
Bruni
Amalia C
AC
D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D002561:Cerebrovascular Disorders / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D006801:Humans; D007558:Italy; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009483:Neuropsychological Tests; D012307:Risk Factors; D014057:Tomography, X-Ray Computed / Q000379:methods
D016564:Amyloid beta-Protein Precursor; D053327:Apolipoprotein E4