Alzheimer's & Senile Dementia

Glycated proteins and free radicals are "partners in crime".

Free radicals and glycation (also called glycosylation) are central to chronic diseases, degeneration and aging. Most people are more familiar with free radicals than glycation, so I try to explain what is is all about.

Glycation occurs in the body when glucose reacts with protein in an undesired way (the Maillard reaction), resulting in sugar-damaged proteins aptly called advanced glycation end products (AGE).

What are AGEs?

AGEs are complexes that progressively damage tissue elasticity since they physically alter proteins, DNA and lipids, changing their chemical properties. Glycation of proteins has been shown to play a prominent role in the development of a number of pathological conditions like diabetic atherosclerosis, diabetic cataract formation, retinopathy and neurological diseases. Glycation causes an increased stiffness in the cardiovascular system leading to high blood pressure.

The formation of AGE happens in everyone and is a major factor in the aging process itself. These damaged proteins may lead to premature signs of aging (wrinkles and brown spots or lipofuscin). Since lipofuscin is composed of protein and carbohydrate, glycation may be involved in lipofuscin formation more than oxidative stress or inflammation. In the long run AGEs exert damaging effects on most organ systems within the body. Glycation reactions are accelerated especially in the diabetic person and contribute to the development of diabetic complications such as arteriosclerosis.

Free radicals and glycation work together

Glycated proteins produce 50-fold more toxic free radicals than nonglycated proteins. As a result of this, AGE exert multiple detrimental effects in the body. For example, AGE induced free radicals activate the proinflammatory cytokine TNF-a (tumor necrosis factor alpha), known to be elevated in the elderly. TNF-a has been shown to be particularly high in inflammatory diseases of the joints (like rheumatoid arthritis), central nervous system (Alzheimer's disease, multiple sclerosis and ischemia) and is considered to promote neurodegeneration.

AGE formation is increased under conditions of oxidative stress, such as glutathione depletion that can for example be found in the substantia nigra in the brain of patients with Parkinson's disease. Glutathione is suggested to be the decisive factor that triggers the formation of Lewy bodies in pre- symptomatic cases of this disease.

AGEs promote Alzheimer´s

Researchers are proposing that AGEs may be part of Alzheimer's disease and present the following evidence to support this hypothesis:

1. AGEs have been found in the neurofibrillary tangles of Alzheimer's disease.
2. Polymerization of beta-amyloid peptide is significantly accelerated by cross-linking through AGEs in vitro.

The inflammatory process is thought to be more important in the progression of neuronal damage eventually resulting in Alzheimer's disease. Because of this, researchers are proposing that AGEs may be a major contributor to the pathogenesis of Alzheimer's disease.

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