2011 Articles

Plasma A and PET PiB binding are inversely related in mild cognitive impairment

Devanand, D. P.; Schupf, N.; Stern, Yaakov; Parsey, R.; Pelton, G. H.; Mehta, P.; Mayeux, R.

Objective: To evaluate the relations between PET Pittsburgh compound B (PiB-PET) binding (amyloid imaging) and plasma A␤ in patients with mild cognitive impairment (MCI) and similarly aged controls. Methods: In 20 patients with MCI and 19 cognitively intact controls (case-control study), PiB binding potential (BPnd) was assessed in 4 regions, and total brain excluding cerebellum, referenced to cerebellar binding. The mean of plasma A␤ levels measured in duplicate was analyzed. Results: Plasma A␤42/A␤40 ratio was decreased in MCI compared to controls (mean 0.15 SD 0.04 vs mean 0.19 SD 0.07, p ϭ 0.03) but A␤40 (p ϭ 0.3) and A␤42 (p ϭ 0.06) levels did not differ between the 2 groups. PiB BPnd was increased in MCI compared to controls in the cingulate (p ϭ 0.02), parietal (p ϭ 0.02), and total brain (p ϭ 0.03), but not in prefrontal cortex (p ϭ 0.08) or parahippocampal gyrus (p ϭ 0.07). Linear regression analyses adjusting for age, sex, and cognitive test scores showed that low A␤42/A␤40 ratio was associated with high cingulate, parietal, and total brain PiB binding (0.01Ͻ p Յ 0.05). These associations between PiB binding and the A␤42/A␤40 ratio were strongest in PiB-positive subjects and within the MCI group. Conclusions: Though cross-sectional, the findings support the “sink” hypothesis that increased brain A␤ is accompanied by lower peripheral levels of A␤, particularly the A␤42/A␤40 ratio in patients with MCI. The association between PiB binding and the plasma A␤42/A␤40 ratio suggests possible use of plasma A␤ combined with PiB binding as a risk biomarker with potential clinical application. Neurology® 2011;77:125–131