Neuronal plasticity in normal aging and deficient plasticity in Alzheimer's disease: A proposed intercellular signal cascade

This chapter examines the evidence for the hypothesis of neuronal plasticity in the normally aging brain and its decrease in Alzheimer's disease (AD) and suggests a cascade of intercellular signals, which may lead to plastic responses of surviving neurons to the death of their neighbors in normally aging brain and which may be affected by AD. The chapter focuses on dendrites as markers of neuronal plasticity, and also considers GAP-43 as a marker of plasticity of the axonal compartment of the neuropil. GAP-43 is associated with plastic responses to injury of the nervous system. Recent data from laboratory indicate that GAP-43 message is reduced in frontal association cortex with increasing age. When AD cases are selected from equivalent age ranges, the level of GAP-43 message in this region of AD brain is not appreciably altered from normal. Whether this reduced GAP-43 in normal aging is entirely attributable to age-related neuron loss remains to be determined.