Plasma biomarkers associated with the apolipoprotein E genotype and Alzheimer disease.
BACKGROUND
A blood-based test that could be used as a screen for Alzheimer disease (AD) may enable early intervention and better access to treatment.


OBJECTIVE
To apply a multiplex immunoassay panel to identify plasma biomarkers of AD using plasma samples from the Alzheimer's Disease Neuroimaging Initiative cohort.


METHODS
Cohort study.


METHODS
The Biomarkers Consortium Alzheimer's Disease Plasma Proteomics Project.


METHODS
Plasma samples at baseline and at 1 year were analyzed from 396 (345 at 1 year) patients with mild cognitive impairment, 112 (97 at 1 year) patients with AD, and 58 (54 at 1 year) healthy control subjects.


METHODS
Multivariate and univariate statistical analyses were used to examine differences across diagnostic groups and relative to the apolipoprotein E (ApoE) genotype.


RESULTS
Increased levels of eotaxin 3, pancreatic polypeptide, and N-terminal protein B-type brain natriuretic peptide were observed in patients, confirming similar changes reported in cerebrospinal fluid samples of patients with AD and MCI. Increases in tenascin C levels and decreases in IgM and ApoE levels were also observed. All participants with Apo ε3/ε4 or ε4/ε4 alleles showed a distinct biochemical profile characterized by low C-reactive protein and ApoE levels and by high cortisol, interleukin 13, apolipoprotein B, and gamma interferon levels. The use of plasma biomarkers improved specificity in differentiating patients with AD from controls, and ApoE plasma levels were lowest in patients whose mild cognitive impairment had progressed to dementia.


CONCLUSIONS
Plasma biomarker results confirm cerebrospinal fluid studies reporting increased levels of pancreatic polypeptide and N-terminal protein B-type brain natriuretic peptide in patients with AD and mild cognitive impairment. Incorporation of plasma biomarkers yielded high sensitivity with improved specificity, supporting their usefulness as a screening tool. The ApoE genotype was associated with a unique biochemical profile irrespective of diagnosis, highlighting the importance of genotype on blood protein profiles.
Bristol-Myers Squibb, Wallingford, CT 06492, USA. Holly.soares@bms.com
Holly D
HD
Soares
William Z
WZ
Potter
Eve
E
Pickering
Max
M
Kuhn
Frederick W
FW
Immermann
David M
DM
Shera
Mats
M
Ferm
Robert A
RA
Dean
Adam J
AJ
Simon
Frank
F
Swenson
Judith A
JA
Siuciak
June
J
Kaplow
Madhav
M
Thambisetty
Panayiotis
P
Zagouras
Walter J
WJ
Koroshetz
Hong I
HI
Wan
John Q
JQ
Trojanowski
Leslie M
LM
Shaw
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics*; D000704:Analysis of Variance; D001055:Apolipoproteins B / Q000097:blood; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000134:cerebrospinal fluid / Q000378:metabolism; D016022:Case-Control Studies; D054370:Chemokine CXCL9 / Q000097:blood; D060825:Cognitive Dysfunction / Q000097:blood / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007118:Immunoassay; D007377:Interleukin-3 / Q000097:blood; D008297:Male; D012372:ROC Curve
D001055:Apolipoproteins B; D001057:Apolipoproteins E; D015415:Biomarkers; C080810:CXCL9 protein, human; D054370:Chemokine CXCL9; D007377:Interleukin-3; D002097:C-Reactive Protein