Senile plaques and neurofibrillary tangles in cortical neurons in AD

Neurodegenerative disorders are characterized clinically by insidious onset and slowly progressive course, and are frequently hereditary. Pathologically, these diseases share a common feature: the selective loss of a particular subset of neurons for unknown reasons [e.g. cerebral cortical neurons in ALZHEIMER’S DISEASE (AD) (see Glossary), substantia nigra neurons in PARKINSON’S DISEASE (PD), spinal motoneurons in AMYOTROPHIC LATERAL SCLEROSIS (ALS), and striatal small neurons in HUNTINGTON’S DISEASE (HD)]. Apoptosis has recently been implicated as a possible mechanism for neuronal death in neurodegenerative diseases. However, there is no direct and convincing evidence of apoptosis in human brains, and the mechanisms of neuronal death in neurodegenerative diseases are still unknown. Here, I will discuss several proposed mechanisms of neuronal death in individual diseases. In addition, I will put forward the concept of a long-standing ‘sick state’ of remaining neurons and the possible underlying mechanisms of neuronal ‘sickness’.