title: Evidence against the overexpression of APP in Down syndrome.
abstract: Down syndrome (DS) is the most common genetic disorder with mental retardation and is caused by trisomy 21. By the age of 40 years, virtually all adults with DS have sufficient neuropathology for a diagnosis of Alzheimer's disease (AD), which is characterized by accumulation of amyloid-beta in senile plaques and formation of neurofibrillary tangles. Amyloid-beta derives from a longer precursor protein, APP, whose gene maps to chromosome 21. In DS, the early appearance of senile plaques is commonly associated with the presence of a third copy of the APP gene. Here we show DS brains and trisomic fibroblasts in which APP is not overexpressed, compared to euploid controls, challenging the notion that the widespread amyloid-beta deposits, consistently found in DS individuals, result from an extra copy of APP.
authors.affiliation: Department of Experimental Medicine, University of Genoa, Genoa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Argellati
authors.forename: Sara
authors.initials: S
authors.lastname: Massone
authors.forename: Cristina
authors.initials: C
authors.lastname: d'Abramo
authors.forename: Umberto M
authors.initials: UM
authors.lastname: Marinari
authors.forename: Maria A
authors.initials: MA
authors.lastname: Pronzato
authors.forename: Cinzia
authors.initials: C
authors.lastname: Domenicotti
authors.forename: Roberta
authors.initials: R
authors.lastname: Ricciarelli
mesh_terms: D000328:Adult; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D004314:Down Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans
chemical_list: D016564:Amyloid beta-Protein Precursor