Clin Psychopharmacol Neurosci.  2017 Feb;15(1):1-8. 10.9758/cpn.2017.15.1.1.

Mechanisms of Alzheimer's Disease Pathogenesis and Prevention: The Brain, Neural Pathology, N-methyl-D-aspartate Receptors, Tau Protein and Other Risk Factors

• Kocahan S
• DoÄŸan Z

• KMID: 2367656
• DOI: http://doi.org/10.9758/cpn.2017.15.1.1

Abstract

The characteristic features of Alzheimer's disease (AD) are the appearance of extracellular amyloid-beta (Aβ) plaques and neurofibrillary tangles in the intracellular environment, neuronal death and the loss of synapses, all of which contribute to cognitive decline in a progressive manner. A number of hypotheses have been advanced to explain AD. Abnormal tau phosphorylation may contribute to the formation of abnormal neurofibrillary structures. Many different structures are susceptible to AD, including the reticular formation, the nuclei in the brain stem (e.g., raphe nucleus), thalamus, hypothalamus, locus ceruleus, amygdala, substantia nigra, striatum, and claustrum. Excitotoxicity results from continuous, low-level activation of N-methyl-D-aspartate (NMDA) receptors. Premature synaptotoxicity, changes in neurotransmitter expression, neurophils loss, accumulation of amyloid β-protein deposits (amyloid/senile plaques), and neuronal loss and brain atrophy are all associated with stages of AD progression. Several recent studies have examined the relationship between Aβ and NMDA receptors. Aβ-induced spine loss is associated with a decrease in glutamate receptors and is dependent upon the calcium-dependent phosphatase calcineurin, which has also been linked to long-term depression.

Keyword

Alzheimer's disease; Amyloid β; N-Methyl-D-Aspartate; Neurodegeneration; Tau; Genetically modified animals

MeSH Terms

Alzheimer Disease*
Amygdala
Amyloid
Animals, Genetically Modified
Atrophy
Basal Ganglia
Brain Stem
Brain*
Calcineurin
Depression
Hypothalamus
Locus Coeruleus
N-Methylaspartate*
Neurofibrillary Tangles
Neurons
Neurotransmitter Agents
Pathology*
Phosphorylation
Receptors, Glutamate
Receptors, N-Methyl-D-Aspartate*
Reticular Formation
Risk Factors*
Spine
Substantia Nigra
Synapses
tau Proteins*
Thalamus
Amyloid
Calcineurin
N-Methylaspartate
Neurotransmitter Agents
Receptors, Glutamate
Receptors, N-Methyl-D-Aspartate
tau Proteins