New Alzheimer’s Blood Markers?

Abstracts & Commentary

Sources: Englehart M, et al. Arch Neurology. 2004;61:668-672; Squitti R, et al. Arch Neurology. 2004;61:738-743.

Inflammation in the brain is one of the established features of the neuropathology of Alzheimer’s Disease (AD). A large case-control study now indicates that patients with elevated serum markers of inflammation have an increased risk of developing AD. The study was based on a prospectively evaluated sample of 727 unaffected individuals and 188 AD cases culled from a larger cohort in the Netherlands. Relative to controls, levels of alpha-1-antichymotrypsin, interleukin-6 and to a lesser extent, C-reactive protein, were found to be elevated in patients who were cognitively intact at baseline but later developed AD. The increase in risk was statistically significant but amounted to less than 50% for each marker. These findings suggest that specific markers of inflammation in the blood may rise before patients develop AD, and might therefore be useful for identifying patients in the general population who are at increased risk of developing AD.

Elevated serum copper levels have been reported in association with AD. Squitti and colleagues previously reported that serum copper levels can be used to distinguish AD from normals and from other forms of dementia. They now report that the AD-affected member of a monozygotic twin pair discordant for dementia had elevated copper levels and indicators of oxidative stress. The twins were 73 years of age when initially studied by cognitive testing, brain imaging, and blood tests. The unaffected twin was documented to remain free of dementia over a 4-year period of follow-up. They found a greater than 40% increase in serum copper and peroxide levels in the affected twin, but no differences in iron, transferrin or homocysteine levels between the 2. The authors believe that the observed elevation in serum copper provides supportive evidence for an abnormality in biometals in AD, and provides encouragement for pursuing further studies of copper levels as a possible diagnostic marker for AD.

Commentary

Blood tests useful for detection of Alzheimer’s have long been sought by AD researchers. Clinical applicability of any such assay requires there be validation and adequate sensitivity and specificity when applied in practice. Neither inflammatory markers in blood or serum copper levels have met these standards, and are unlikely to become stand-alone AD diagnostic tests. These reports provide useful information nevertheless. The elevations observed in blood markers of inflammation could be indicative of inflammation in the brain or of a more generalized systemic process in patients at risk for AD. Elevations in copper speak to the possible involvement of metals in the disease process. Moreover, both inflammation and copper levels can be reduced by available interventions, which could provide new inroads for development of future treatments for AD. While these biomarkers are not ready for general clinical use, they could prove useful in the future. — Norman R. Relkin

Dr. Relkin, Associate Professor of Clinical Neurology and Neuroscience, New York, Presbyterian Hospital-Cornell Campus, is Assistant Editor of Neurology Alert.