Neurodegenerative Diseases: Pathology and the Advantage of Single-Cell Profiling

The aggregation of neuronal proteins as inclusions is emerging as a common mechanistic theme in neurodegenerative diseases. The presence of these "disease-specific" pathologic changes in the brains of patients with neurodegenerative diseases assist pathologists in the diagnosis and characterization of dementing illnesses. However, these same inclusions may provide valuable clues toward understanding common pathologic roots and shared abnormalities in protein folding across disorders. Such an investigation will likely provide insights into disease mechanisms underlying neurodegenerative disorders characterized by abundant filamentous lesions. This review focuses on two themes: (i) Neurodegenerative disorders are characterized by shared and distinct histopathological and biochemical abnormalities, and (ii) the presence of abnormal protein aggregates may alter a gene, and hence protein expression in inclusion-bearing neurons predisposes them to dysfunction and eventual neuronal degeneration. The pathologic features of neurodegenerative diseases are first discussed followed by a rationale behind sampling mRNA species from single cells rather than from whole-brain homogenates to explore disease mechanisms.