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

European Journal of Human Genetics : EJHG
Lina KellerCaroline Graff

Abstract

Early-onset dominantly inherited forms of Alzheimer's disease (AD) are rare, but studies of such cases have revealed important information about the disease mechanisms. Importantly, mutations in amyloid precursor protein (APP), presenilin 1 (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 pathogenic mechanisms, show that Aβ42 is a major player in the etiology of AD. 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 AD. We also performed an extensive investigation on 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.

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Citations

Feb 15, 2013·PloS One·Anna SandebringLars O Tjernberg
Feb 26, 2014·Neuropharmacology·Maoping TangZhongdong Qiao
Jan 28, 2016·Brain : a Journal of Neurology·Elena Rodriguez-VieitezAgneta Nordberg
Apr 12, 2015·Acta Neuropathologica·Sylvie BurnoufLinda Partridge
Jan 13, 2017·Journal of the International Neuropsychological Society : JINS·Ove AlmkvistCaroline Graff
Dec 3, 2016·Journal of Alzheimer's Disease : JAD·Xiaozhen LiCaroline Graff
Jul 5, 2011·Nature Neuroscience·Takashi SaitoTakaomi C Saido
Feb 3, 2015·Journal of Internal Medicine·X LiC Graff
Apr 5, 2018·Journal of Alzheimer's Disease : JAD·Steinunn Thordardottir, Caroline Graff
May 12, 2021·Acta Neuropathologica Communications·Alejandro Ruiz-RiquelmeJoel C Watts

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