An overview of Alzheimer's disease-related content on Genes to Cognition Online.

Alzheimer’s disease is a progressive brain disorder that causes a gradual and irreversible loss of higher brain functions, including memory, language skills, and perception of time and space, and, eventually, leading to an inability to care for oneself. Use Background to Alzheimer’s to review the symptoms causes, and treatments of the disorder. The three hallmarks of Alzheimer’s disease are amyloid plaques, neurofibrillary tangles, and death of brain cells. The fundamental pathogenesis of Alzheimer’s disease is the plaque and the amyloid deposition. Then, secondarily, the amyloid triggers this reaction in cells to form tangles. GENES Use the chromosome Map of Disorders and Processes to explore some of the candidate genes associated with Alzheimer’s disease. One of these genes, amyloid precursor protein (APP), is widely expressed in tissues, and is particularly expressed in the synapses of neurons. It is particularly associated with earl-onset Alzheimer’s disease. A primary cause of Alzheimer’s disease is deposits of a protein called amyloid-beta as plaques in the brain. When multiple amyloid beta peptides come together, they form an insoluble piece of protein called an amyloid plaque. Tau is the protein that is formed in the neurofibrillary tangle. The purpose of this system of tau and microtubules is for moving cargo down along axons. In a series of illuminating interviews, Professors Kenneth Kosic, Dennis Selkoe, and Donna Wilcock discuss the molecular processes associated with Alzheimer’s disease. BIOCHEMICALS In the Biochemistry of Alzheimer's Disease, Professor Donna Wilcock explains that neurotransmitter hypotheses of Alzheimer's disease are largely unspecific. Nevertheless, glutamate, serotonin, and NPY have elicited interest. Aricept is the principle biochemical used to treat Alzheimer's disease, but can only postpone progression. Professor Dennis Selkoe explains that treatments in the coming years are likely to become more effective. CELLS Amyloid-beta (a-beta) build-up causes amyloid plaques. A-beta oligomers can short circuit the synapses in the hippocampus, and interfere with long-term potentiation, a major correlate of memory and learning. Amyloid triggers this reaction in cells to form neurofibrillary tangles. This is made up of the tau protein, and forms inside the cell. When tangles clump up inside the cell, this causes the neuron to become stressed and eventually die. Thus, there is largely a linear relationship between a-beta build-up, tangles, and neuronal death. Inevitably, this leads to major cognitive problems. BRAIN In Alzheimer’s Neuropathology – Stages, Professor Donna Wilcock introduces Braak and Braak staging, which refers to the movement of pathology of Alzheimer’s disease throughout the brain. In the earliest stages of Alzheimer’s disease, you see the pathology in the hippocampus and entorhinal cortex, which are important to memory formation. had for breakfast that the hippocampus does – this is the formation of new memories. Eventually, this spreads to the rest of the brain affecting sensory-processing areas and the amygdala, which processes emotions. Interestingly, some regions of the brain, such as the cerebellum, are not affected. COGNITION The major risk factor for Alzheimer’s disease is age – among individuals of 65, 5-10% have the disorder. This statistic rises to approximately 40% for those aged 85 years or older. It follows that as the general population ages, incidence will rise, and may affect up to 14 million Americans by 2050. Currently, up to 6 million people in the United States have Alzheimer’s disease, which has two forms – late-onset, which is the far more common and early-onset, which is rare and affects individuals between 35 and 60. Alzheimer’s disease is diagnosed clinically by a battery of tests, but it may be possible to use neuroimaging as a diagnostic tool in the near future. ENVIRONMENT The Dana review article, Environment and Alzheimer’s Disease, discusses environmental factors including diet, exercise, red wine consumption, and low stress, which may lower the risk of Alzheimer’s disease. In addition, a number of studies have shown a correlation between higher levels of education and resistance to Alzheimer’s disease. This is sometimes known as the ‘use it or lose it idea’, but remains somewhat controversial among researchers.