NIH: ApoE in blood may indicate early Alzheimers risk

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The amount of apolipoprotein E (ApoE) measured in blood tests may be associated with amyloid-B deposition in the brain, an early indicator of Alzheimer's disease (AD), presenting the possibility of early and more accessible testing for the disease, according to research published Dec. 22, 2010, in the Journal of Alzheimer's Disease.

"Amyloid-B deposition within the brain is a key event in Alzheimer's disease pathogenesis, preceding the onset of symptoms," wrote Madhav Thambisetty, MD, of the National Institute on Aging in Baltimore, and colleagues. Brain amyloid-B (AB) burden can be observed using Pittsburgh Compound B (C-PiB) tracing of AB in PET scans, but the test is a costly and unlikely method for routine AD screening.

"The aim of the present study was to identify a blood-based signature of in vivo brain amyloid deposition through proteomic analysis of plasma in non-demented older adults," noted Thambisetty and co-authors. Thambisetty and colleagues used proteomics technology to analyze blood samples from 57 elderly, symptom-free volunteers to identify specific proteins that were associated with AB in the brain, as measured by C-PiB PET.

Thambisetty and co-researchers found that the amount of ApoE in participants' blood was strongly associated with the level of AB in the brain. Participants with greater concentrations of ApoE had significantly higher AB burdens in the medial temporal cortex, as viewed using C-PiB PET scans conducted 10 years prior, with a demographics-adjusted correlation of .46.

In PET scans conducted within one year of the blood work, plasma ApoE concentrations were likewise significantly associated with greater PiB retention in the hippocampus bilaterally, the right parahippocampal gyrus and the entorhinal cortex, confirming the ApoE association.

"These results are especially intriguing as this protein [ApoE] is made by the ApoE gene, the most robust genetic risk factor for late-onset Alzheimer's," Thambisetty commented. An association between ApoE concentration and genetic carriers of the ApoE gene could indicate higher risk for AD. The authors acknowledged, however, that their small sample size precluded robust analysis of the relationship between ApoE and AB burden in the brain.

Thambisetty expressed his intention to test these findings yearly by conducting serial blood samples in the Baltimore Longitudinal Study of Aging participants to determine the relationship between changing ApoE levels in the blood and pathological changes. "If the results are equally positive, we may be able to develop a blood test that provides a less invasive, inexpensive method that helps to detect the early pathological changes of Alzheimer's disease," Thambisetty said.