Serum sphingomyelins and ceramides are early predictors of memory impairment

被引:136
作者
Mielke, Michelle M. [1 ,4 ]
Bandaru, Veera Venkata Ratnam [2 ]
Haughey, Norman J. [2 ]
Rabins, Peter V. [1 ]
Lyketsos, Constantine G. [1 ]
Carlson, Michelle C. [3 ,4 ]
机构
[1] Johns Hopkins Univ, Sch Med, Dept Psychiat, Div Geriatr Psychiat & Neuropsychiat, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Ctr Aging & Hlth, Baltimore, MD 21205 USA
[4] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21205 USA
关键词
Sphingomyelins; Ceramides; Serum lipid markers; Memory; Alzheimer's disease; Biomarker; ALZHEIMERS-DISEASE; RISK-FACTORS; CHOLESTEROL; PLASMA; ASSOCIATION; INVOLVEMENT; METABOLISM; EXPRESSION; DEMENTIA; NEURONS;
D O I
10.1016/j.neurobiolaging.2008.03.011
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
A blood-based biomarker of Alzheimer's disease (AD) progression could be instrumental in targeting asymptomatic individuals for treatment early in the disease process. Given the direct connection between sphingomyelins (SM), ceramides, and apoptosis, these lipids maybe indicators of neurodegeneration and AD progression. Baseline serum SM and ceramides from 100 women enrolled in a longitudinal population-based study were examined as predictors of cognitive impairment. Participants were followed up to six visits over 9 years. Baseline lipids, in tertiles, were examined in relation to cross-sectional and incident impairment (<1.5 S.D. below standard norms) on HVLT-immediate and -delayed memory recall and Trails A and B. SM and ceramides varied in relation to the timing of HVLT-delayed impairment: low levels were associated with cross-sectional impairment; high levels predicted incident impairment in asymptomatic individuals. Lipids were not associated with loss-to-follow-up. Results suggest serum SM and ceramides vary according to the timing of the onset of memory impairment and may be good pre-clinical predictors, or biomarkers, of memory impairment: a deficit observed early in AD pathogenesis. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:17 / 24
页数:8
相关论文
共 32 条
[21]   Lipids and the pathogenesis of Alzheimer's disease: Is there a link? [J].
Mielke, M. M. ;
Lyketsos, C. G. .
INTERNATIONAL REVIEW OF PSYCHIATRY, 2006, 18 (02) :173-186
[22]   High total cholesterol levels in late life associated with a reduced risk of dementia [J].
Mielke, MM ;
Zandi, PP ;
Sjögren, M ;
Gustafson, D ;
Östling, S ;
Steen, B ;
Skoog, I .
NEUROLOGY, 2005, 64 (10) :1689-1695
[23]   ELASTIC-DEFORMATION AND FAILURE OF LIPID BILAYER-MEMBRANES CONTAINING CHOLESTEROL [J].
NEEDHAM, D ;
NUNN, RS .
BIOPHYSICAL JOURNAL, 1990, 58 (04) :997-1009
[24]   Plasma sphingomyelin and subclinical atherosclerosis: Findings from the multi-ethnic study of atherosclerosis [J].
Nelson, J ;
Jiang, XC ;
Tabas, I ;
Tall, A ;
Shea, S .
AMERICAN JOURNAL OF EPIDEMIOLOGY, 2006, 163 (10) :903-912
[25]   Brain membrane phospholipid alterations in Alzheimer's disease [J].
Pettegrew, JW ;
Panchalingam, K ;
Hamilton, RL ;
McClure, RJ .
NEUROCHEMICAL RESEARCH, 2001, 26 (07) :771-782
[26]   CORRELATION OF P-31 MAGNETIC-RESONANCE SPECTROSCOPY AND MORPHOLOGIC FINDINGS IN ALZHEIMERS-DISEASE [J].
PETTEGREW, JW ;
PANCHALINGAM, K ;
MOOSSY, J ;
MARTINEZ, J ;
RAO, G ;
BOLLER, F .
ARCHIVES OF NEUROLOGY, 1988, 45 (10) :1093-1096
[27]   Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins [J].
Ray, Sandip ;
Britschgi, Markus ;
Herbert, Charles ;
Takeda-Uchimura, Yoshiko ;
Boxer, Adam ;
Blennow, Kaj ;
Friedman, Leah F. ;
Galasko, Douglas R. ;
Jutel, Marek ;
Karydas, Anna ;
Kaye, Jeffrey A. ;
Leszek, Jerzy ;
Miller, Bruce L. ;
Minthon, Lennart ;
Quinn, Joseph F. ;
Rabinovici, Gil D. ;
Robinson, William H. ;
Sabbagh, Marwan N. ;
So, Yuen T. ;
Sparks, D. Larry ;
Tabaton, Massimo ;
Tinklenberg, Jared ;
Yesavage, Jerome A. ;
Tibshirani, Robert ;
Wyss-Coray, Tony .
NATURE MEDICINE, 2007, 13 (11) :1359-1362
[28]   Astroglial expression of ceramide in Alzheimer's disease brains: A role during neuronal apoptosis [J].
Satoi, H ;
Tomimoto, H ;
Ohtani, R ;
Kitano, T ;
Kondo, T ;
Watanabe, M ;
Oka, N ;
Akiguchi, I ;
Furuya, S ;
Hirabayashi, Y ;
Okazaki, T .
NEUROSCIENCE, 2005, 130 (03) :657-666
[29]   Cholesterol depletion inhibits the generation of β-amyloid in hippocampal neurons [J].
Simons, M ;
Keller, P ;
De Strooper, B ;
Beyreuther, K ;
Dotti, CG ;
Simons, K .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (11) :6460-6464
[30]   INDUCTION OF ALZHEIMER-LIKE BETA-AMYLOID IMMUNOREACTIVITY IN THE BRAINS OF RABBITS WITH DIETARY-CHOLESTEROL [J].
SPARKS, DL ;
SCHEFF, SW ;
HUNSAKER, JC ;
LIU, HC ;
LANDERS, T ;
GROSS, DR .
EXPERIMENTAL NEUROLOGY, 1994, 126 (01) :88-94