4 - Neurochemical aspects of memory dysfunction in neurodegenerative disease

Summary

INTRODUCTION

The relationship between ‘classical’ neuroanatomy and what has been termed the ‘chemoarchitecture’ of the brain is formidably complex, and discussions of that relationship always run the risk of oversimplification. Patterns of selective cell degeneration have been described in certain exemplary disorders (Alzheimer's, Parkinson's and Huntington's diseases), and yet such observations only inform Nieuwenhuys' important caveat that neuromediatorspecified neuronal populations do not obey simple rules (Nieuwenhuys 1985).

This chapter addresses the major neurochemical changes in three archetypal degenerative disorders – Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD) – in the context of a review of ‘classical’ and ‘chemical’ neuroanatomies pertinent to each. Some implications for a neurochemical understanding of normal memory are discussed at the chapter's conclusion.

ANATOMICAL AND NEUROTRANSMITTER CONSIDERATIONS

Alzheimer's disease

Large cholinergic neurons populate several structures in the basal forebrain that in essence form a continuum, including the nucleus basalis of Meynert, nuclei of the diagonal band of Broca and the medial septal nucleus. Mesulam divided the forebrain cholinergic neuronal population into four major groups (Mesulam et al. 1983), of which Ch4 (roughly corresponding to the nucleus basalis of Meynert, but also including cholinergic neurons located within the internal and external medullary laminae of the globus pallidus) is of particular interest.

Cholinergic innervation of the neocortex and amygdala derives largely from Ch4 (Struble et al. 1986) and, in turn, Ch4 receives reciprocal cortical innervation from ‘limbic’ structures, including orbitofrontal, medial and polar temporal, prepiriform and entorhinal cortices (Mesulam and Mufson 1984). Loss of cholinergic neurons particularly in the nucleus basalis is characteristic in AD, though by no means the only hallmark of the disease (Whitehouse et al. 1981, 1982).