Portal de Periódicos da CAPES

P3‐286: Subcortical ischemic vascular dementia: A search for APP gene mutations

2008; Wiley; Volume: 4; Issue: 4S_Part_18 Linguagem: Inglês

10.1016/j.jalz.2008.05.1854

1552-5279

Silvana Geracitano, Livia Bernardi, Raffaele Maletta, Carmine Tomaino, Maura Gallo, Maria Anfossi, Franca Vasso, Rosanna Colao, Gianfranco Puccio, Francesca Frangipane, Maria Mirabelli, Nicoletta Smirne, Maria Gabriella Muraca, Ornella De Vito, Teresa Dattilo, Michele Menniti, Amalia C. Bruni,

Alzheimer's disease research and treatments

Mutations in the amyloid precursor protein (APP) gene can cause clinically distinct entities, such as autosomal dominant forms of Alzheimer's disease (AD), Hereditary cerebral hemorrhage with amyloidosis (HCHWA) and Cerebral amyloid angiopathy (CAA). However, mutations in exons 16 and 17 may lead also to AD with CAA. We previously reported the APP A713T mutation associated with AD and subcortical ischemic lesions at MRI in a large family in which neuropathology evidenced CAA and AD lesions. Since a common pathological hallmark of Alzheimer's disease and cerebral amyloid angiopathy (CAA) is the deposition of amyloid β (Aβ) in parenchymal senile plaques and cerebral blood vessel walls, we investigated APP gene in patients affected by familial Subcortical Ischemic Vascular Dementia (SIVD). Thirty-two consecutive unrelated persons (20 females and 12 males; average onset age: 71.8±6.6 years) were diagnosed as affected by familial SIVD. Familiarity was established through history; all patients showed at least a first/second degree relative affected. Exons 15–18 of APP gene were analyzed by sequencing in the affected subjects. Sequence of APP exon 17 revealed in three patient the same A713T mutation already published by our group in a large family segregating with AD and CAA. Pathogenic role of the APP A713T mutation is once again confirmed. Further genealogical and molecular studies will be necessary to determine whether a common ancestor does exist linking our patient to the family previously reported. Moreover, a molecular screening of APP gene exons 15–18 could be helpful also in patients affected by familial SIVD that could be caused by Cerebral amyloid angiopathy.