A novel presenilin-1 mutation: increased beta-amyloid and neurofibrillary changes

Annals of Neurology
T Gómez-IslaR Tanzi

Abstract

The prevalence of known mutations in presenilin genes (PS1 and PS2) causing early-onset familial Alzheimer's disease (FAD) was assessed in a population of 98 singleton early-onset AD cases, 29 early-onset FAD cases, and 15 late-onset FAD cases. None of the cases tested positive for the eight mutations initially reported, and none of these mutations were observed in 60 age-matched controls. A novel mutation (R269H) in PS1 was found in a single case of early-onset AD but not in any other AD or control case. Thus, the PS mutations tested are quite rare in early-onset AD. Amyloid beta protein (A beta) deposition was investigated in the temporal cortex of the R269H mutation case using end-specific monoclonal antibodies to detect the presence of A beta x-40 and A beta x-42 subspecies. Stereologically unbiased tangle and neuropil thread counts were obtained from the same region. R269H PS1 mutation was associated with early age of dementia onset, higher amounts of total A beta and A beta x-42, and increased neuronal cytoskeletal changes. Thus, if the changes observed on this case prove to be typical of PS1 mutations, PS1 mutations may impact both amyloid deposition and neurofibrillary pathology.

References

Nov 1, 1985·Archives of Neurology·Z S Khachaturian
Sep 1, 1995·Nature Medicine·W WascoD M Kovacs
Jun 1, 1996·Neurobiology of Disease·R E TanziW Wasco

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Citations

Mar 24, 2009·Acta Neuropathologica·Claire ShepherdGlenda Margaret Halliday
May 17, 2005·Neurobiology of Aging·Gillian C GregoryGlenda M Halliday
Nov 6, 1998·Journal of the Neurological Sciences·K KamimuraT Tabira
Jul 25, 2000·Psychiatry Research·K OharaK Ohara
Oct 24, 2002·Neurobiology of Aging·Gianluigi ForloniAlessandro Bertoli
Feb 7, 1998·Current Opinion in Neurobiology·T W Kim, R E Tanzi
May 18, 2011·ACS Chemical Neuroscience·Masahiro OnoHideo Saji
Jun 21, 2011·Brain : a Journal of Neurology·Natalie S RyanJonathan M Schott
Sep 10, 2002·Alzheimer Disease and Associated Disorders·Guilian XuDavid R Borchelt
Apr 11, 2013·Dementia and Geriatric Cognitive Disorders·Mira DidicMathieu Ceccaldi
May 4, 2006·The Journal of Clinical Psychiatry·Andreas PapassotiropoulosEric M Reiman
Aug 5, 1998·Proceedings of the National Academy of Sciences of the United States of America·A TakashimaB Wolozin
Dec 26, 2006·Journal of the Neurological Sciences·A J LarnerM Doran
Aug 1, 2014·Frontiers in Molecular Neuroscience·Taeko KimuraShin-Ichi Hisanaga
Oct 25, 2016·Neurobiology of Aging·Steffan K SoosmanJohn M Ringman
Oct 3, 2006·Brain : a Journal of Neurology·Christian R A MondadoriKatharina Henke
Jul 9, 2008·Annals of Medicine·Nathalie BrouwersChristine Van Broeckhoven
Jan 5, 2011·Annals of Neurology·Yakeel T QuirozChantal E Stern
Apr 1, 1998·Human Mutation·M Cruts, C Van Broeckhoven
Apr 18, 2018·BMC Bioinformatics·Yingxue RenYan W Asmann
Jun 20, 2020·Neurotoxicity Research·Md Tanvir KabirMohamed M Abdel-Daim
Aug 1, 2021·The American Journal of Pathology·Rajesh N Kalaria, Diego Sepulveda-Falla
Jun 8, 2001·The American Journal of Pathology·D M MannUNKNOWN Members of the Familial Alzheimer's Disease Pathology Study Group

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