TY - JOUR
T1 - A novel pathogenic PSEN1 mutation in a family with Alzheimer's disease
T2 - Phenotypical and neuropathological features
AU - Gallo, Maura
AU - Marcello, Norina
AU - Curcio, Sabrina A M
AU - Colao, Rosanna
AU - Geracitano, Silvana
AU - Bernardi, Livia
AU - Anfossi, Maria
AU - Puccio, Gianfranco
AU - Frangipane, Francesca
AU - Clodomiro, Alessandra
AU - Mirabelli, Maria
AU - Vasso, Franca
AU - Smirne, Nicoletta
AU - Muraca, Gabriella
AU - Di Lorenzo, Raffaele
AU - Maletta, Raffaele
AU - Ghidoni, Enrico
AU - Bugiani, Orso
AU - Tagliavini, Fabrizio
AU - Giaccone, Giorgio
AU - Bruni, Amalia C.
PY - 2011
Y1 - 2011
N2 - We report a novel presenilin1 (PSEN1) gene mutation (I143 V) in a four-generation family with Alzheimer's disease. Clinical, molecular, and neuropathological examinations were performed on index patient; thirteen affected subjects were also identified. The index patient presented at 55 with personality changes, apathy, reduction of verbal fluency, and temporal and spatial disorientation. At 68, she showed visual hallucinations; blurred language, and rigidity. She became bedridden and died at 75. A novel mutation at codon 143 was found in PSEN1 gene, changing isoleucine to valine. The brain showed severe atrophy of the frontal and temporal lobes. Parenchymal amyloid-β (Aβ) deposits were abundant, diffuse to grey structures and contained Aβ42, but very few Aβ40. Amyloid angiopathy was absent. Neurofibrillary changes were severe. Our study confirms that PSEN1 mutations can be associated with unusual phenotypes. The peculiarity of the age at onset (not very early), the long course, and the frontal involvement, together with the rather complete absence of Aβ40 and of amyloid angiopathy, widen the spectrum of PSEN1-linked phenotypes.
AB - We report a novel presenilin1 (PSEN1) gene mutation (I143 V) in a four-generation family with Alzheimer's disease. Clinical, molecular, and neuropathological examinations were performed on index patient; thirteen affected subjects were also identified. The index patient presented at 55 with personality changes, apathy, reduction of verbal fluency, and temporal and spatial disorientation. At 68, she showed visual hallucinations; blurred language, and rigidity. She became bedridden and died at 75. A novel mutation at codon 143 was found in PSEN1 gene, changing isoleucine to valine. The brain showed severe atrophy of the frontal and temporal lobes. Parenchymal amyloid-β (Aβ) deposits were abundant, diffuse to grey structures and contained Aβ42, but very few Aβ40. Amyloid angiopathy was absent. Neurofibrillary changes were severe. Our study confirms that PSEN1 mutations can be associated with unusual phenotypes. The peculiarity of the age at onset (not very early), the long course, and the frontal involvement, together with the rather complete absence of Aβ40 and of amyloid angiopathy, widen the spectrum of PSEN1-linked phenotypes.
KW - Alzheimer's disease
KW - neurodegeneration
KW - neuropathology
KW - PSEN1 mutation
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UR - http://www.scopus.com/inward/citedby.url?scp=79960817329&partnerID=8YFLogxK
U2 - 10.3233/JAD-2011-110185
DO - 10.3233/JAD-2011-110185
M3 - Article
C2 - 21422519
AN - SCOPUS:79960817329
VL - 25
SP - 425
EP - 431
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
SN - 1387-2877
IS - 3
ER -