Peripheral monocytes are functionally altered and invade the CNS in ALS patients

Area of Science:

• Neuroimmunology
• Neurodegenerative Diseases

Background:

• Amyotrophic lateral sclerosis (ALS) involves neuroinflammation in the central nervous system (CNS).
• The role of the peripheral immune system in ALS pathogenesis is not well understood.
• Peripheral monocytes' interaction with CNS immune cells in motor neuron degeneration requires further investigation.

Purpose of the Study:

• To characterize peripheral monocytes in amyotrophic lateral sclerosis (ALS) pathogenesis.
• To investigate the role of peripheral monocytes in motor neuron survival.
• To explore therapeutic strategies targeting peripheral monocytes in ALS.

Main Methods:

• Characterization of circulating monocyte subtypes, function, and gene expression in ALS.
• Assessment of CNS infiltration of peripheral monocytes in a genetic ALS mouse model.
• Evaluation of human immunoglobulins and Fc-containing fusion proteins for their effect on monocyte infiltration and disease onset.

Main Results:

• Circulating monocytes exhibit deregulation in ALS concerning subtype, function, and gene expression.
• Increased CNS infiltration of peripheral monocytes correlates with enhanced motor neuron survival in an ALS mouse model.
• Human immunoglobulins and Fc fragments promote monocyte CNS invasion and delay disease onset.

Conclusions:

• Peripheral monocytes play a significant role in ALS pathogenesis.
• Monocytes may exert a protective effect in the early stages of ALS.
• Targeting peripheral monocyte function, potentially with human immunoglobulins, warrants clinical evaluation for ALS treatment.