Pathophysiology and Treatment of Alzheimer's Disease

Dear Colleagues,

The cure for any condition in medicine requires addressing the causal elements that contribute to its pathogenesis. The causal elements that contribute to the pathogenesis of Alzheimer’s dementia (AD) are numerous; their precise number depends on how they are counted, but they certainly number 15 or more. These causal elements include neural tracts and dendrites and synapses and neurotransmitters, that in turn are the ultimate cause of dementia but that result from interactions with astrocytic, microglial, and endothelial pathologies; involvement of genetics and epigenetics; mitochondrial impairments; inflammation, both cerebral and systemic; intracellular biochemical determinants including calcium dynamics; the role of the endoplasmic reticulum; the roles of the unfolded protein response and autophagy; the important functions of intracellular organelles without membranes; and finally, the importance of physical chemistry, e.g., liquid–liquid phase separation.

With all of this knowledge, it is surprising that no cure for AD has been found. Clearly, there are several reasons for this failure. A major reason is that a cure would require using several drugs, and almost all clinical trials tested the effects of only single drugs. Another reason is that the number of drugs needed to address all of the causal factors is so large that they cannot be concurrently administered.

Nevertheless, it cannot be beyond human ingenuity to find a cure for Alzheimer’s dementia. That is why the International Journal of Molecular Science has issued a challenge to the community of neuroscientists and others, to contribute their ideas to this Special Issue of the journal, that will be devoted to the task of devising a way that will allow dementia sufferers to resume their lives with normal memory and cognition.

Prof. Dr. Jeffrey Fessel
Guest Editor

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• Alzheimer's disease
• Alzheimer’s dementia
• neurodegeneration
• AD
• pathogenesis
• cure for AD