Blood-based neurochemical diagnosis of vascular dementia: a pilot study.
Blood-based tests for the differential diagnosis of Alzheimer's disease (AD) are under intensive investigation and have shown promising results with regard to Abeta40 and Abeta42 peptide species in incipient AD. Moreover, plasma Abeta40 was suggested as an independent cerebrovascular risk factor candidate. These considerations prompted us to analyse a total of 72 plasma samples in vascular dementias (VAD, n = 15), AD with cerebrovascular disease (AD with CVD, n = 7), AD (n = 15), Parkinson's disease and Parkinson's disease dementia (PD/PDD, n = 20) and 15 patients with depression that served as controls (DC) for distinct plasma amyloid-beta (Abeta) peptide patterns. For the analysis of plasma we used immunoprecipitation followed by the quantitative Abeta-SDS-PAGE/immunoblot. For comparison, CSF tau and Abeta1-42 analyses were performed. The major outcome was an increase in Abeta1-40 in plasma of VAD paralleled by a decrease in the ratio of Abeta1-38/Abeta1-40. The ratio Abeta1-38/Abeta1-40 in plasma enabled contrasts of beyond 85% and 80% for discriminating VAD from DC and all other patients, respectively. In CSF, we confirmed the typical CSF biomarker constellation of increased tau and diminished Abeta1-42 levels for AD. The diagnostic accuracy of plasma Abeta1-38/Abeta1-40 for VAD resembled the accuracy of CSF biomarkers for AD. From the presented results, we consider the ratio of plasma Abeta1-38/Abeta1-40 peptides to be a blood-based biomarker candidate for VAD.
Department of Psychiatry University of Goettingen, von-Siebold-Str, Goettingen, Germany. mbibl@gwdg.de
Mirko
M
Bibl
Hermann
H
Esselmann
Brit
B
Mollenhauer
Godehard
G
Weniger
Volker
V
Welge
Michael
M
Liess
Piotr
P
Lewczuk
Markus
M
Otto
Jörg B
JB
Schulz
Claudia
C
Trenkwalder
Johannes
J
Kornhuber
Jens
J
Wiltfang
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid; D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid; D015415:Biomarkers; D002561:Cerebrovascular Disorders / Q000097:blood / Q000134:cerebrospinal fluid; D003704:Dementia / Q000209:etiology / Q000523:psychology; D015140:Dementia, Vascular / Q000097:blood* / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D003866:Depressive Disorder / Q000097:blood; D003937:Diagnosis, Differential; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood / Q000150:complications / Q000523:psychology; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010865:Pilot Projects; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins