Evolution of Abeta42 and Abeta40 levels and Abeta42/Abeta40 ratio in plasma during progression of Alzheimer's disease: a multicenter assessment.
OBJECTIVE
To better understand the seemingly contradictory plasma beta-amyloid (Abeta) results in Alzheimer's disease (AD) patients by using a newly developed plasma Abeta assay, the INNO-BIA plasma Abeta forms, in a multicenter study.


METHODS
A combined retrospective analysis of plasma Abeta isoforms on mild cognitive impairment (MCI) from three large cross-sectional studies involving 643 samples from the participating German and Swedish centers.


RESULTS
Detection modules based on two different amino (N)-terminal specific Abeta monoclonal antibodies demonstrated that Abeta in plasma could be reliable quantified using a sandwich immunoassay technology with high precision, even for low Abeta42 plasma concentrations. Abeta40 and Abeta42 concentrations varied consistently with the ApoE genotype, while the Abeta42/Abeta40 ratio did not. Irrespective of the decrease of the Abeta42/Abeta40 ratio with age and MMSE, this parameter was strongly associated with AD, as defined in this study by elevated hyperphosphorylated (P-tau181P) levels in cerebrospinal fluid (CSF).


CONCLUSIONS
A highly robust assay for repeatedly measuring Abeta forms in plasma such as INNO-BIA plasma Abeta forms might be a useful tool in a future risk assessment of AD.
Blennow
K
K
Sahlgrenska University Hospital, Göteborg University, Sweden.
De Meyer
G
G
Hansson
O
O
Minthon
L
L
Wallin
A
A
Zetterberg
H
H
Lewczuk
P
P
Vanderstichele
H
H
Vanmechelen
E
E
Kornhuber
J
J
Wiltfang
J
J
Heuser
I
I
Maier
W
W
Luckhaus
C
C
Rüther
E
E
Hüll
M
M
Jahn
H
H
Gertz
H J
HJ
Frölich
L
L
Hampel
H
H
Pernetzki
R
R
D000368:Aged; D000375:Aging; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005858:Germany; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000097:blood*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D018570:Risk Assessment; D013548:Sweden
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)