A Novel Pathogenic PSEN1 Mutation in a Family with Alzheimer's Disease: Phenotypical and Neuropathological Features

Article type: Research Article

Authors: Gallo, Maura^{a; 1} | Marcello, Norina^{b; 1} | Curcio, Sabrina A.M.^a | Colao, Rosanna^a | Geracitano, Silvana^a | Bernardi, Livia^a | Anfossi, Maria^a | Puccio, Gianfranco^a | Frangipane, Francesca^a | Clodomiro, Alessandra^a | Mirabelli, Maria^a | Vasso, Franca^a | Smirne, Nicoletta^a | Muraca, Gabriella^a | Di Lorenzo, Raffaele^a | Maletta, Raffaele^a | Ghidoni, Enrico^b | Bugiani, Orso^c | Tagliavini, Fabrizio^c | Giaccone, Giorgio^c | Bruni, Amalia C.^{a; *}

Affiliations: [a] Centro Regionale di Neurogenetica, ASP Catanzaro, Lamezia Terme (CZ), Italy | [b] U.O. Neurologia, Arcispedale S. Maria Nuova, Reggio Emilia, Italy | [c] Dipartimento di Neuropatologia-Neurologia 5, Fondazione IRCCS Istituto Neurologico Besta, Milano, Italy

Correspondence: [*] Correspondence to: 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: bruni@arn.it.

Note: [1] These authors contributed equally to this work.

Abstract: 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.

Keywords: Alzheimer's disease, neurodegeneration, neuropathology, PSEN1 mutation

DOI: 10.3233/JAD-2011-110185

Journal: Journal of Alzheimer's Disease, vol. 25, no. 3, pp. 425-431, 2011