Shared and Unique Disease Pathways in Amyotrophic Lateral Sclerosis and Parkinson’s Disease Unveiled in Peripheral Blood Mononuclear Cells

Recent evidence supports
an association between amyotrophic lateral
sclerosis (ALS) and Parkinson’s disease (PD). Indeed, prospective
population-based studies demonstrated that about one-third of ALS
patients develop parkinsonian (PK) signs, even though different neuronal
circuitries are involved. In this context, proteomics represents a
valuable tool to identify unique and shared pathological pathways.
Here, we used two-dimensional electrophoresis to obtain the proteomic
profile of peripheral blood mononuclear cells (PBMCs) from PD and
ALS patients including a small cohort of ALS patients with parkinsonian
signs (ALS-PK). After the removal of protein spots correlating with
confounding factors, we applied a sparse partial least square discriminant
analysis followed by recursive feature elimination to obtain two protein
classifiers able to discriminate (i) PD and ALS patients (30 spots)
and (ii) ALS-PK patients among all ALS subjects (20 spots). Functionally,
the glycolysis pathway was significantly overrepresented in the first
signature, while extracellular interactions and intracellular signaling
were enriched in the second signature. These results represent molecular
evidence at the periphery for the classification of ALS-PK as ALS
patients that manifest parkinsonian signs, rather than comorbid patients
suffering from both ALS and PD. Moreover, we confirmed that low levels
of fibrinogen in PBMCs is a characteristic feature of PD, also when
compared with another movement disorder. Collectively, we provide
evidence that peripheral protein signatures are a tool to differentially
investigate neurodegenerative diseases and highlight altered biochemical
pathways.