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.
References
Aug 1, 1992·Nature Genetics·M MullanL Lannfelt
Jan 1, 1991·Cerebral Cortex·S E ArnoldG W Van Hoesen
Jan 1, 1991·Neurology·J J MartinU Lübke
Jun 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·C L MastersK Beyreuther
May 16, 1984·Biochemical and Biophysical Research Communications·G G Glenner, C W Wong
Oct 1, 1995·Nature Genetics
Mar 31, 1995·The Journal of Biological Chemistry·S A GravinaS G Younkin
Jul 1, 1994·Neuron·T IwatsuboY Ihara
May 11, 1993·Biochemistry·J T JarrettP T Lansbury
Dec 1, 1995·Human Molecular Genetics·M CrutsP Cras
Nov 1, 1996·Neuron·D R BorcheltS S Sisodia
Jan 1, 1997·Nature Medicine·M CitronD J Selkoe
Mar 1, 1997·Nature Medicine·A M ChinnaiyanG J Nabel
Jan 27, 1999·Annals of Medicine·M Cruts, C Van Broeckhoven
Mar 29, 2001·Physiological Reviews·D J Selkoe
Aug 29, 2001·Neurology·E A RogaevaP St George-Hyslop
Aug 31, 2001·Nature Neuroscience·C NilsberthL Lannfelt
Sep 25, 2001·American Journal of Medical Genetics·D ArangoM Jacquier
Jul 20, 2002·Science·John Hardy, Dennis J Selkoe
Jul 22, 2005·Journal of Medical Genetics·G RauxD Campion
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Yosuke NagasakaCaroline Graff
Jun 6, 2006·Human Mutation·Samir Kumar-SinghChristine Van Broeckhoven
Sep 6, 2007·Neuron·Jorge J PalopLennart Mucke
Oct 31, 2007·Neurogenetics·Noritoshi AraiShoji Tsuji
Sep 24, 2008·Neurogenetics·Laura FilonziFrancesco Nonnis Marzano
Feb 11, 2009·Archives of Neurology·Jorge J Palop, Lennart Mucke
May 22, 2009·Journal of Neurochemistry·Hedvig WelanderLars O Tjernberg
Aug 29, 2012·Biochemical and Biophysical Research Communications·George G Glenner, Caine W Wong
Citations
Nov 3, 2011·BMC Research Notes·Håkan ThonbergCaroline Graff
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
Dec 8, 2017·Scientific Reports·Elisabetta Lauretti, Domenico Praticò
Aug 5, 2017·Nursing & Health Sciences·Mette BergmanKerstin S Fugl-Meyer
Feb 1, 2018·Molecular Neurobiology·Raquel CoronelIsabel Liste
Aug 10, 2018·Aging and Disease·Yangqi XuHuidong Tang
Jul 5, 2011·Nature Neuroscience·Takashi SaitoTakaomi C Saido
Feb 23, 2017·Frontiers in Aging Neuroscience·Ina S AlmdahlTormod Fladby
Feb 3, 2015·Journal of Internal Medicine·X LiC Graff
Jul 14, 2017·Frontiers in Aging Neuroscience·Camilla LauridsenLinda R White
Apr 5, 2018·Journal of Alzheimer's Disease : JAD·Steinunn Thordardottir, Caroline Graff
Apr 9, 2013·The American Journal of Pathology·Kun ZouHiroto Komano
May 12, 2021·Acta Neuropathologica Communications·Alejandro Ruiz-RiquelmeJoel C Watts
Jun 3, 2021·Nutrients·Afsana TajmimKhalid A El Sayed
May 23, 2021·Journal of Internal Medicine·D O T AlawodeH Zetterberg