Plasma multianalyte profiling in mild cognitive impairment and Alzheimer disease

被引：200

作者：

Hu, William T. ^{[1
,2
,9
]}

Holtzman, David M. ^{[7
,8
]}

Fagan, Anne M. ^{[7
,8
]}

Shaw, Leslie M. ^{[2
,4
]}

Perrin, Richard ^{[8
]}

Arnold, Steven E. ^{[3
,5
]}

Grossman, Murray ^{[1
]}

Xiong, Chengjie ^{[8
]}

Craig-Schapiro, Rebecca ^{[7
,8
]}

Clark, Christopher M. ^{[10
]}

Pickering, Eve ^{[11
]}

Kuhn, Max ^{[11
]}

Chen, Yu ^{[11
]}

Van Deerlin, Vivianna M. ^{[2
,4
]}

McCluskey, Leo ^{[1
]}

Elman, Lauren ^{[1
]}

Karlawish, Jason ^{[6
]}

Chen-Plotkin, Alice ^{[1
,2
]}

Hurtig, Howard I. ^{[1
]}

Siderowf, Andrew ^{[1
]}

Swenson, Frank ^{[11
]}

Lee, Virginia M-Y. ^{[2
,4
,5
]}

Morris, John C. ^{[7
,8
]}

Trojanowski, John Q. ^{[2
,4
,5
]}

Soares, Holly ^{[12
]}

机构：

[1] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA

[2] Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA

[3] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA

[4] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[5] Univ Penn, Sch Med, Inst Aging, Philadelphia, PA 19104 USA

[6] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA

[7] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA

[8] Washington Univ, Sch Med, Knight Alzheimers Dis Res Ctr, St Louis, MO USA

[9] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA

[10] Avid Pharmaceut, Philadelphia, PA USA

[11] Pfizer Global Res & Dev, Groton, CT USA

[12] Bristol Myers Squibb Co, New London, CT USA

来源：

NEUROLOGY | 2012年 / 79卷 / 09期

基金：

美国国家卫生研究院;

关键词：

FRONTOTEMPORAL LOBAR DEGENERATION; NEUROIMAGING INITIATIVE SUBJECTS; BRAIN NATRIURETIC PEPTIDE; PANCREATIC-POLYPEPTIDE; CLINICAL CHARACTERIZATION; BIOMARKERS; DIAGNOSIS; DEMENTIA; CLASSIFICATION; PREDICTION;

D O I：

10.1212/WNL.0b013e318266fa70

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Objectives: While plasma biomarkers have been proposed to aid in the clinical diagnosis of Alzheimer disease (AD), few biomarkers have been validated in independent patient cohorts. Here we aim to determine plasma biomarkers associated with AD in 2 independent cohorts and validate the findings in the multicenter Alzheimer's Disease Neuroimaging Initiative (ADNI). Methods: Using a targeted proteomic approach, we measured levels of 190 plasma proteins and peptides in 600 participants from 2 independent centers (University of Pennsylvania, Philadelphia; Washington University, St. Louis, MO), and identified 17 analytes associated with the diagnosis of very mild dementia/mild cognitive impairment (MCI) or AD. Four analytes (apoE, B-type natriuretic peptide, C-reactive protein, pancreatic polypeptide) were also found to be altered in clinical MCI/AD in the ADNI cohort (n = 566). Regression analysis showed CSF A beta 42 levels and t-tau/A beta 42 ratios to correlate with the number of APOE4 alleles and plasma levels of B-type natriuretic peptide and pancreatic polypeptide. Conclusion: Four plasma analytes were consistently associated with the diagnosis of very mild dementia/MCI/AD in 3 independent clinical cohorts. These plasma biomarkers may predict underlying AD through their association with CSF AD biomarkers, and the association between plasma and CSF amyloid biomarkers needs to be confirmed in a prospective study. Neurology (R) 2012;79:897-905

引用

页码：897 / 905

页数：9

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