Sequence of deposition of heterogeneous amyloid beta-peptides and APO E in Down syndrome: implications for initial events in amyloid plaque formation

Neurobiology of Disease
Cynthia A LemereD J Selkoe

Abstract

Patients with trisomy 21 [Down syndrome (DS)] progressively develop amyloid beta-protein (A beta) deposits and then other features of Alzheimer's disease (AD), apparently due to increased gene dosage and thus expression of the beta-amyloid precursor protein. Because the neuropathological phenotype in older DS subjects closely resembles that of AD, the examination of DS brains of increasing age provides a unique model of the progression of AD. Here, we characterized the deposition of several A beta peptides and apolipoprotein E in formalin-fixed brain sections from 29 DS subjects between 3 and 73 years old. Amyloid plaque number and the percentage of cortical area they occupied were quantified by computerized image analysis. A beta ending at amino acid 42 (A beta 42) was the earliest form of A beta deposited in DS cortex. It was observed in 7 of 16 young (3-30 years) subjects, with the earliest deposition occurring at age 12. A beta ending at residue 40 (A beta 40) was not detected until approximately age 30, a time when degenerating neurites around A beta immunoreactive (IR) plaques were first observed, and the frequency of A beta 40 IR plaques then rose with age. Even in old (51-73 years) DS subjects, A beta 42 IR plaques were...Continue Reading

Citations

Apr 1, 2010·Acta Neuropathologica·Gunnar K GourasEstibaliz Capetillo-Zarate
Dec 17, 2009·Brain Structure & Function·Thomas Wisniewski, Allal Boutajangout
Jul 29, 2005·The American Journal of Pathology·Samir Kumar-SinghChristine Van Broeckhoven
Jan 7, 2000·The American Journal of Pathology·G K GourasN R Relkin
Feb 10, 2000·The American Journal of Pathology·S E StoltznerC A Lemere
Sep 9, 2011·Nature Medicine·Dennis J Selkoe
Jul 1, 1997·Nature Medicine·M K LeeS S Sisodia
Jun 7, 2000·Neuropathology and Applied Neurobiology·K HorsburghJ A Nicoll
Oct 4, 2011·The Journal of Biological Chemistry·Sadim JawharThomas A Bayer
May 22, 2010·Brain : a Journal of Neurology·Lena JohanssonIngmar Skoog
Aug 7, 2012·Human Molecular Genetics·Jessica E Young, Lawrence S B Goldstein
May 18, 2011·Cold Spring Harbor Perspectives in Biology·Dennis J Selkoe
Feb 22, 2012·Science Translational Medicine·Yichen ShiFrederick J Livesey
Feb 3, 1999·Annual Review of Genetics·D L PriceS S Sisodia
Jul 27, 2002·Annual Review of Genomics and Human Genetics·Dennis J Selkoe, Marcia B Podlisny
Apr 8, 1998·Annual Review of Neuroscience·D L Price, S S Sisodia
Nov 5, 2002·Annual Review of Pharmacology and Toxicology·Dennis J Selkoe, Dale Schenk
Jan 18, 2006·Dementia and Geriatric Cognitive Disorders·Scott E CountsElliott J Mufson
Apr 13, 2007·Neuro-degenerative Diseases·Verena H Finder, Rudi Glockshuber
Jan 4, 2003·The Journal of Clinical Investigation·Todd E Golde
Nov 4, 2010·Journal of Geriatric Psychiatry and Neurology·Lynn M BekrisDebby W Tsuang
Aug 14, 2009·Alzheimer's Research & Therapy·Paul S Aisen
May 27, 2010·PloS One·Juliet A MoncasterLee E Goldstein
Feb 17, 2011·Immunotherapy·Salim Shah, Howard J Federoff
May 27, 2009·International Journal of Molecular Sciences·Samir Kumar-Singh
Feb 13, 2014·Brain : a Journal of Neurology·M Florencia IulitaA Claudio Cuello
Mar 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·R P FriedlandS M Debanne
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·C RussoM Tabaton
Aug 23, 2001·Proceedings of the National Academy of Sciences of the United States of America·A MonsonegoH L Weiner
Dec 28, 1999·Proceedings of the National Academy of Sciences of the United States of America·K R BalesS M Paul
Apr 20, 2005·Proceedings of the National Academy of Sciences of the United States of America·M A KingsburyJ Chun

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alzheimer's Disease: APOE

Apolipoprotein E (APOE) polymorphic alleles are major genetic risk factors for Alzheimer's disease. Discover the latest research on APOE and other genetic determinants of Alzheimer's disease here.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

ApoE Phenotypes

Apolipoprotein E (APOE) is a protein involved in fat metabolism and associated with the pathogenesis of Alzheimer's disease and cardiovascular disease. Here is the latest research on APOE phenotypes.