Neuroanatomy/pathology and the interplay of neurotransmitters in moderate to severe Alzheimer disease
Paul T. Francis, PhD From the Wolfson Centre for Age-Related Diseases and the GKT School of Biomedical Science, King’s College London, London, England.
Alzheimer disease (AD) is a progressive neurodegenerative disease that leads to the permanent loss of neurons and synapses. Neuron loss, particularly affecting glutamatergic pyramidal neurons, is prominent in the neocortex and hippocampus, areas of particular importance in memory, cognition, and function (ref.1) Neuron loss in AD may be profound in subcortical structures, with neuronal degeneration in regions such as the nucleus basalis of Meynert (nbM) exceeding 75% (ref.2). In the healthy brain, the neuron population in the nbM is approximately 500,000 to 600,000 cells. However, as AD progresses into the more severe stages, the number of neurons in this region is significantly decreased to 100,000 cells (ref.3) It should be noted that this change in neuron numbers may represent loss of neurochemical phenotype as well as overt cell loss. Whatever the cause, deficits in cholinergic innervation of the cortex and hippocampus—which accompany synapse loss or dysfunction in these areas of the brain—are believed to be important in the development and progression of AD (ref.1).
In addition to death of neurons, the pathologic hallmarks of AD include the presence of senile plaques (SPs) and neurofibrillary tangles (NFTs) in the cortex, hippocampus, and other regions of the brain (ref.4), (ref.5). Neuron and synapse loss, together with the formation of SPs and NFTs, cause significant changes in many neurotransmitter systems, including the cholinergic and glutamatergic neurotransmitter systems (ref.6), (ref.7).
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