The PSEN1 I143T mutation in a Swedish family with Alzheimer disease: Clinical report and quantification of Aβ in different brain regions

Caroline Graff (1) , Lina Keller (1) , Hedvig Welander (1) , Huei-Hsin Chiang (1) , Lars O Tjernberg (1) , Inger Nennesmo (1) , Åsa K Wallin (1)

1 Department of Neurobiology, Caring Sciences and Society (NVS)

Early onset dominantly-inherited forms of Alzheimer disease are rare, but studies of such cases have revealed important information about the disease mechanisms. Importantly, mutations in APP, PSEN1 and PSEN2, alter the APP processing and lead to an increased amyloid β-peptide (Aβ) 42/40 ratio. This, together with other studies on the pathogenic mechanisms, show that Aβ42 is a major player in the etiology of Alzheimer disease. Here we present a clinical and neuropathological description of a Swedish family with an I143T mutation in the PSEN1 gene, which gives rise to a severe form of Alzheimer disease. We also performed an extensive investigation of the concentration and distribution of Aβ species of different lengths in six brain regions from two mutation-carriers. Our study showed that Aβ42 and a longer peptide, Aβ43, were present both in plaque cores and in total amyloid preparations, and were each clearly more frequent than Aβ40 in all examined regions, as shown by both mass spectrometry and immunohistochemistry.

Mots clés: Alzheimer disease; PSEN1 mutations; amyloid β-peptide variants

Caroline Graff, Lina Keller, Hedvig Welander, Huei-Hsin Chiang, Lars O Tjernberg, et al.. The PSEN1 I143T mutation in a Swedish family with Alzheimer disease: Clinical report and quantification of Aβ in different brain regions. European Journal of Human Genetics, 2010, ⟨10.1038/ejhg.2010.107⟩. ⟨hal-00555618⟩