Peripheral Abeta subspecies as risk biomarkers of Alzheimer's disease.
Plasma Abeta42 and Abeta40 levels are putative biomarkers for Alzheimer's disease (AD), but their significance and predictive value have been inconclusive. In AD transgenic models, plasma and cerebrospinal fluid levels of Abeta42 and Abeta40 increase with age but subsequently decrease when Abeta begins to accumulate in brain and with the onset of cognitive impairment. To determine the predictive value of Abeta levels in elderly populations, we investigated how plasma Abeta42, Abeta40, and a protofibrillar subspecies of Abeta42 changed over time and with the onset of cognitive impairment or AD. In a cohort of 1,125 elderly persons without dementia, 104 (9.2%) of the participants developed AD over 4.6 years of follow-up. Higher plasma Abeta42 levels at the onset of the study were associated with a threefold increased risk of AD. However, conversion to AD was accompanied by a significant decline in plasma Abeta42, a decreased Abeta42/Abeta40 ratio and, with the onset of cognitive impairment, decreased protofibrillar Abeta42 levels. Our results suggest individuals with elevated plasma Abeta42 are at increased risk of AD and that with the onset of disease, the decline in some forms of Abeta may reflect compartmentalization of Abeta peptides in the brain.
Schupf
Nicole
N
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Tang
Ming X
MX
Fukuyama
Hide
H
Manly
Jennifer
J
Andrews
Howard
H
Mehta
Pankaj
P
Ravetch
Jeffery
J
Mayeux
Richard
R
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D015415:Biomarkers; D005260:Female; D006801:Humans; D008297:Male; D012307:Risk Factors
D016229:Amyloid beta-Peptides; D015415:Biomarkers
J Lipid Res. 1990 Mar;31(3):545-8
2341813
Proc Natl Acad Sci U S A. 1998 May 26;95(11):6448-53
9600986
Arch Neurol. 2007 Jul;64(7):1007-13
17620492
Dement Geriatr Cogn Disord. 2007;23(5):316-20
17374949
Annu Rev Neurosci. 1994;17:489-517
8210185
Ann Neurol. 1999 Sep;46(3):412-6
10482274
Nature. 2006 Mar 16;440(7082):352-7
16541076
Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3675-9
8170968
Ann Neurol. 1995 Feb;37(2):254-9
7847867
Ann Neurol. 1996 Aug;40(2):149-56
8773595
Mol Med. 2001 Sep;7(9):609-18
11778650
J Biol Chem. 1997 Aug 29;272(35):22364-72
9268388
Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10417-22
12925731
J Neurosci. 2001 Jan 15;21(2):372-81
11160418
Neurology. 2008 Feb 19;70(8):596-606
17914065
Lancet Neurol. 2003 Oct;2(10):605-13
14505582
J Psychiatr Res. 1975 Nov;12(3):189-98
1202204
J Neurosci. 2000 Jun 1;20(11):4050-8
10818140
Arch Neurol. 2007 Mar;64(3):354-62
17353377
Neuroscience. 2008 Feb 6;151(3):745-9
18155846
Ann Neurol. 2006 Mar;59(3):512-9
16372280
JAMA. 1998 Mar 11;279(10):751-5
9508150
Lancet Neurol. 2006 Aug;5(8):655-60
16857570
Neurobiol Aging. 2002 Mar-Apr;23(2):231-5
11804707
Neurology. 1997 Mar;48(3):741-5
9065558
Neurology. 2004 Sep 14;63(5):828-31
15365131
Ann Neurol. 1998 Jul;44(1):17-26
9667589
Nature. 2002 Apr 4;416(6880):535-9
11932745
Arch Neurol. 2003 Jul;60(7):958-64
12873852
Br J Psychiatry. 1982 Jun;140:566-72
7104545
Arch Neurol. 2008 Feb;65(2):256-63
18268197
JAMA. 2000 Mar 22-29;283(12):1571-7
10735393
J Clin Invest. 2005 May;115(5):1121-9
15864339
Nat Med. 1996 Aug;2(8):864-70
8705854
Arch Neurol. 2000 Jan;57(1):100-5
10634455
Neurology. 1984 Jul;34(7):939-44
6610841
Neurology. 2003 Nov 11;61(9):1185-90
14610118
Arch Neurol. 1992 May;49(5):453-60
1580806
Am J Geriatr Psychiatry. 2005 Oct;13(10):914-7
16223971
Neurosci Lett. 2001 Apr 6;301(3):199-203
11257432
Arch Neurol. 2007 Mar;64(3):343-9
17210801
Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2273-6
15695586
Arch Neurol. 1992 May;49(5):461-7
1580807
Neurology. 1974 Nov;24(11):1019-25
4473151