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

Objective: To evaluate the relations between PET Pittsburgh compound B (PiB-PET) binding (amyloid imaging) and plasma A beta 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 beta levels measured in duplicate was analyzed. Results: Plasma A beta 42/A beta 40 ratio was decreased in MCI compared to controls (mean 0.15 SD 0.04 vs mean 0.19 SD 0.07, p = 0.03) but A beta 40 (p = 0.3) and A beta 42 (p = 0.06) levels did not differ between the 2 groups. PiB BPnd was increased in MCI compared to controls in the cingulate (p = 0.02), parietal (p = 0.02), and total brain (p = 0.03), but not in prefrontal cortex (p = 0.08) or parahippocampal gyrus (p = 0.07). Linear regression analyses adjusting for age, sex, and cognitive test scores showed that low A beta 42/A beta 40 ratio was associated with high cingulate, parietal, and total brain PiB binding (0.01 < p <= 0.05). These associations between PiB binding and the A beta 42/A beta 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 beta is accompanied by lower peripheral levels of A beta, particularly the A beta 42/A beta 40 ratio in patients with MCI. The association between PiB binding and the plasma A beta 42/A beta 40 ratio suggests possible use of plasma A beta combined with PiB binding as a risk biomarker with potential clinical application. Neurology(R) 2011;77:125-131