Reduced cystatin C in CSF can reflect UMN involvement as shown in high-field MR of ALS, potentially providing a new biomarker for UMN degeneration in ALS.
However, the staining intensities of CST3 and PSAP decreased in Bunina body-positive motor neurons of patients with amyotrophic lateral sclerosis (ALS).
Novel intracytoplasmic inclusions immunoreactive for phosphorylated transactivation response DNA-binding protein 43 (p-TDP43), cystatin C, and transferrin were found in anterior horn cells in a case of sporadic amyotrophic lateral sclerosis (ALS).
Interestingly, we report for the first time pathological hallmarks of SPG11 in neurons that include intracytoplasmic granular lysosome-like structures mainly in supratentorial areas, and others in subtentorial areas that are partially reminiscent of those observed in amyotrophic lateral sclerosis, such as ubiquitin and p62 aggregates, except that they are never labelled with anti-TDP-43 or anti-cystatin C. The neuropathological overlap with amyotrophic lateral sclerosis, associated with some shared clinical manifestations, opens up new fields of investigation in the physiopathological continuum of motor neuron degeneration.
They also showed regional cytoplasmic transactive response deoxyribonucleic acid-binding protein 43 mislocalization with loss of nuclear transactive response deoxyribonucleic acid-binding protein 43 staining in the lateral nuclear group of spinal cord innervating distal hand muscles and cystatin C-positive cytoplasmic aggregates, reminiscent of the spinal cord pathology of patients with amyotrophic lateral sclerosis.
The present data demonstrate that the level of CC in CSF should not be considered as a biomarker of ALS, but there is a correlation between CC levels and the CST3 genotype.
The results reported here indicate that there may not be a direct genetic link between cystatin C and ALS, and it may be that deficits occur in proteins that interact with cystatin C.