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Is ammonia a pathogenetic factor in Alzheimer's disease?

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Abstract

An attempt was made to review experimental evidence in favor of the idea that ammonia plays a role in dementia of the Alzheimer type (DAT). Hyperammonemia causes biochemical and cellular dysfunctions in the brain, which can be found in brains of DAT patients. The most conspicuous among these findings are astrocytosis, impairment of glucose utilization, and a decreased rate of energy metabolism, and the impairment of neurotransmission, with a net increase in excitability and glutamate release. The derangement of lysosomal processing of proteins is another potential site of ammonia action. This aspect is especially important in view of the growing evidence for the role of the endosomal-lysosomal system in the formation of amyloidogenic fragments from β-amyloid precursor protein. Ammonia is not considered a primary factor of the disease. However, since hyperammonemia and release of ammonia from the brains of DAT patients is well supported by published observations, ammonia should be taken into account as a factor that contributes to manifestations and the progression of DAT. If elevated ammonia concentrations turn out to be indeed as important in DAT, as is suggested in this review, rational therapeutic avenues can be envisaged that lead to the amelioration of symptoms and progression of the disease.

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Abbreviations

β-AP:

β-amyloid protein

β-APP:

β-amyloid precursor protein

CNS:

central nervous system

DAT:

dementia of the Alzheimer type

GABA:

γ-aminobutyrate

MAO:

monoamine oxidase

NAD:

nicotinamide adenine dinucleotide

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  1. Marion Merrell Dow Research Institute, Strasbourg, France

    Nikolaus Seiler

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This paper is dedicated to Rudi Vrba, a pioneer of the neurochemistry of ammonia, and a friend, at the occasion of his 68th birthday.

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Seiler, N. Is ammonia a pathogenetic factor in Alzheimer's disease?. Neurochem Res 18, 235–245 (1993). https://doi.org/10.1007/BF00969079

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