Evaluation of heme oxygenase-1 as a systemic biological marker of sporadicAD

Background: Heme oxygenase-1 (HO-1) is a 32-kDa stress protein that catalyz es the degradation of heme to biliverdin. HO-1 immunoreactivity is greatly increased in neurons and astrocytes of the hippocampus and cerebral cortex of individuals with AD and colocalizes to senile plaques and neurofibrillar y tangles. Methods: We investigated whether systemic HO-1 regulation is als o deranged in AD patients and whether blood HO-1 measurements provide a per ipheral biomarker of the disease. Plasma HO-1 protein levels were measured by competitive ELISA and lymphocyte HO-1 mRNA levels were determined by Nor thern analysis in patients with early probable sporadic AD, normal elderly controls (NEC), normal younger controls, individuals with age-associated co gnitive decline (AACD) not meeting AD criteria, and patients with non-Alzhe imer dementia, nondementing neurologic illness, and chronic medical disorde rs. CSF HO-1 protein concentrations were also determined by ELISA in pathol ogically confirmed AD and control cases. Results: Mean plasma HO-1 protein concentrations were significantly lower in AD patients (0.85 +/- 0.14 mu g/ mL) compared with NEC (1.77 +/- 0.34 mu g/mL; p < 0.05) and control patient s. The AACD group exhibited plasma HO-1 concentrations (1.06 +/- 0.33 mu g/ mL) intermediate between, but not different from, those of the AD patients and NEC. Lymphocyte HO-1 mRNA levels were lower in the AD cohort relative t o NEC (p < 0.001) and individuals with AACD, non-Alzheimer dementia, nondem enting neurologic illness, and chronic medical conditions. Lymphocyte HO-1 mRNA levels were also lower in the AACD group relative to NEC (p < 0.05). I n comparison with all groups excluding AACD, the sensitivity and specificit y of lymphocyte HO-1 mRNA measurement for diagnosis of early sporadic AD ar e 88% and 75%. Mean CSF HO-1 protein concentrations were lower (p < 0.01) i n AD cases (19.07 ng/mL) relative to control values (32.48 ng/mL). Conclusi ons: Plasma and CSF HO-1 protein and lymphocyte HO-1 mRNA levels are decrea sed in subjects with sporadic AD. Quantitative assay for lymphocyte HO-1 mR NA expression may serve as a useful biologic marker in early sporadic AD.