Occurrence of reduced alpha 2-macroglobulin and lowered protease inhibiting capacity in plasma of amyotrophic lateral sclerosis patients.

Lowered levels of plasma alpha 2-macroglobulin were found in 13 patients with amyotrophic lateral sclerosis using anti-alpha 2-macroglobulin-embedded agar plates. Levels of this major protease inhibitor in ALS patients were contrasted with those in disease controls, consisting of patients with a variety of neurologic disorders, as well as with those in normal individuals. The patients' levels, in milligrams per deciliter, were 191 +/- 39 (SD). The disease controls had levels of 269 +/- 33. Local normal values compared with the reported normal values in the literature (260 +/- 70). A correlation was not made for either the form of motor neuron disease, disease severity, or age. As a measure of functional protease inhibition, trypsin inhibitory capacity of sera was estimated using a radioactive fibrinolytic assay. An increase in the half-maximal inhibitory concentration of sera was found in the amyotrophic lateral sclerosis group. These findings likely relate to the known increases in proteolytic activity in denervated muscle and collagenolytic activity in skin of patients with amyotrophic lateral sclerosis. The determination of whether altered protease inhibitory potential in such patients is primary or secondary may help in understanding the pathogenesis of this enigmatic disorder and provide suggestions for future approaches to intervention.