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. 2013 Apr 5:5:15.
doi: 10.3389/fnagi.2013.00015. eCollection 2013.

Evaluation of annexin A5 as a biomarker for Alzheimer's disease and dementia with lewy bodies

Hitoshi Sohma  1 , Shin-Ichi Imai, Norio Takei, Hirohito Honda, Kyoichi Matsumoto, Kumiko Utsumi, Kayo Matsuki, Eri Hashimoto, Toshikazu Saito, Yasuo Kokai
Affiliations

Evaluation of annexin A5 as a biomarker for Alzheimer's disease and dementia with lewy bodies

Hitoshi Sohma et al. Front Aging Neurosci. .

Abstract

Background: Alzheimer's disease (AD) differs from other forms of dementia in its relation to amyloid beta peptide (Aβ42). Using a cell culture model we previously identified annexin A5, a Ca(2+), and phospholipid binding protein, as an AD biomarker. Plasma level of annexin A5 was significantly higher in AD patients compared to that in a control group. On the other hand, AD has been identified to share a number of clinical and pathological features with Dementia with Lewy bodies (DLB). The present study was done to examine whether or not plasma annexin A5 is a specific marker for AD, when being compared with the levels of DLB patients. As Apolipoprotein E (ApoE) gene subtype ε4 (ApoE-ε4) has been noticed as the probable genetic factor for AD, we also examined and compared ApoE genotype in both AD and DLB.

Methods: Blood samples were obtained from 150 patients with AD (aged 77.6 ± 6.5 years), 50 patients of DLB (79.4 ± 5.0) and 279 community-dwelling healthy elderly individuals of comparable age and sex (75.6 ± 8.1). All AD patients met NINCDS-ADRDA criteria and all DLB patients were diagnosed as probable DLB according to the latest consensus diagnostic criteria. Quantification was done using the Chemiluminescent Enzyme Immunoassay (CLEIA) Technique (SphereLight assay) using the monoclonal antibodies against annexin A5. DNA genotyping of ApoE was performed by distinguishing unique combinations of Hha1 fragments of PCR-amplified genomic DNA products.

Results: The plasma level of annexin A5 was significantly higher in AD patients than in the healthy individuals (control) (P < 0.0001). The plasma annexin A5 level was also significantly higher in DLB patients than in the control group (P < 0.0001). From the ROC curves with plasma annexin A5 concentrations, the mean areas under the curve were 0.863 and 0.838 for the AD/control and DLB/control, respectively. The rate of ApoE4 carrier status and the frequency of the ε4 allele were significantly higher in AD or DLB than in control and there was no significant difference between AD and DLB.

Conclusions: These results suggest that both annexin A5 and ApoE4 are common markers for AD and DLB.

Keywords: Alzheimer's disease; ApoE; Ca2+-stress; ROC curve; annexin A5; dementia with lewy bodies; plasma biomarker.

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Figures

Figure 1
Figure 1
Comparison of plasma levels of annexin A5 in AD, DLB patients, and healthy volunteers (control). For quantitative analysis, we established a chemiluminescent enzyme immunoassay system with monoclonal antibodies against human annexin A5 and measured human plasma annexin A5. Dot blot is shown. Each point represents the plasma annexin A5 concentration of individual. AD, Alzheimer's disease; DLB, dementia with Lewy bodies.
Figure 2
Figure 2
Receiver operating characteristic (ROC) curves showing prediction of either AD or DLB by plasma annexin A5. The probability of either AD or DLB can be predicted by a logistic regression model with the plasma level of annexin A5. The areas under the curve are 86.3 and 83.8% for AD and DLB, respectively. AD, Alzheimer's disease; DLB, dementia with Lewy bodies.
Figure 3
Figure 3
ApoE carrier statuses of AD (A), DLB (B), and healthy volunteers (control) (C). ApoE carrier statuses are significantly different between AD and control, and between DLB and control. However, no significant differences were observed between AD and DLB. ApoE typing was done using pcr and restriction enzyme digestion using genomic DNA. AD, Alzheimer's disease; DLB, dementia with Lewy bodies.
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