Pathology of ALS Sample Clauses

Pathology of ALS. ‌ The classic pathological hallmarks of ALS are the degeneration and loss of motor neurons together with astrocytosis and intracellular aggregates in degenerating motor neurons and glia. UMN pathology is characterized by the loss of Xxxx cells and astrocytosis in the motor cortex accompanied by axonal loss and myelin pallor within the descending pyramidal motor pathway (Xxxxxx et al., 1979; Xxxx et al., 1987; Xxxxxxx et al., 1995). LMN pathology affects the ventral horn of the spinal cord and the motor neurons in the brainstem. Autopsy findings include a reduced number of LMN and reactive astrocytosis (Xxxxxx et al., 1993; Xxxxxxxxxx et al., 1979). The surviving neurons are atrophic and contain 3 types of intraneuronal inclusions: Bunina bodies, neurofilament accumulations and ubiquitinated inclusions. Bunina bodies are cytoplasmic eosinophilic inclusions initially described by the Russian neuropathologist Xxxxxx who suspected them to be the sign of a viral infection (Xxxxxx, 1962). Found mostly in the remaining LMN, Bunina bodies are present in approximately 85% of ALS cases and are generally considered a specific pathologic finding (Piao et al., 2003). They are thought to be of lysosomal origin and are seen more frequently in patients with shorter disease durations and patients with dementia and ALS (Xxxxxxx et al., 2008). Cystatin C, transferrin and more recently peripherin have been identified as major components of these inclusions but despite numerous investigations, their origin and significance are still unclear (Mizuno et al., 2006; Mizuno et al., 2011; Xxxxxxx et al., 1993). Another long known feature of ALS is the accumulation of phosphorylated neurofilaments and peripherin in affected motor neuron perikarya and their proximal axons (Xxxxxxxxx, 1968; Xxxxx and Hays, 1992; Xxxxxx et al., 1984; Xxxxx et al., 1988). However, these inclusions are not specific to ALS, since aberrant accumulation of neurofilaments occurs in other neurodegenerative diseases including Xxxxxxxxx’x disease, dementia with Lewy bodies, Alzheimer’s disease and progressive supranuclear palsy (Xx-Xxxxxxx and Xxxxxx, 2003). The association with other conditions suggests they might play a role in disease pathogenesis, a hypothesis supported by the finding that point mutations in the light neurofilament subunit gene cause forms of the sensory and motor neuropathy Charcot-Xxxxx-Tooth disease (Mersiyanova et al., 2000). Interestingly, modulation of neurofilament expression in ALS t...