Cause, Pathology and Treatment of Alzheimer's Disease

Cause, Pathology and Treatment of Alzheimer's Disease
Growing up in the 80's I remember my mother questioning President Reagan's politics, policies, morality, and even his sanity. Though I would not wish a debilitating disease on anyone, I had to laugh at the irony when I heard Reagan had Alzheimer's Disease(AD). To think that his "I do not recall" line during the Contra scandal may have been true! The idea of the President of the United States suffering the early stages of a disease causing dementia, confusion, irritability, and memory loss(1) during the very dangerous Cold War gives me the heebie jeebies.
Symptoms(6,7) Reagan and the Cold War aside, Alzheimer's is an appalling disease, affecting millions of people, with no known cure. Even the cause is not fully understood. Its symptoms are memory loss, confusion, poor judgment, personality changes, and loss of intellectual competence. The disease progresses, leaving victims unable to care for themselves. Patients usually die between 8 and 20 years after onset. The emotional strain of the victims who can feel the deterioration of their minds, as well as the family and friends who witness it are often devastating.

Pathology(2, 3) AD is characterized by the death of acetylcholine (a neurotransmitter) secreting cells. The major pathological description of AD is Neurofibrillary tangles(NFTs). Though NFTs normally exist in elderly people, the high quantity and distribution in AD patients is unique. NFTs are fibrous tangles that grow out of the neuronal soma and extend into the dendrites. These tangles remain, even after the parent cell is killed and deteriorates. NFTs are composed of strands of insoluble proteins, twisted into a helix called PHFs of about 20 nm. These helixes are complexed with 15 nm strands of straight filaments. interestingly PHFs are composed of altered forms of microtubule subunits, though their form is distinct. Other characteristic attributes of an AD brain are Neuritic plaques, surrounded by enlarged axons, dendrites, and synaptic terminals. These plaques are formed from beta-amyloid, an abnormal protein.

Cause(4) The cause of AD is very controversial. Though the pathology can be recognized, the cause of AD is still very mysterious. The severity of AD seems to be directly related to the quantity of NFTs. NFTs are caused by over-phosphorylation of a normal brain protein called Tau, which normally assists in forming the shape of neuron processes, such as axons and dendrites. However, why over-phosphorylation occurs is still unknown. Some scientists think that it and all other symptoms will be traced back to a specific protein: beta-amyloid, the protein which forms Neuritic plaques. In fact some studies indicate that "deposition of beta-amyloid can initiate the disease"(4). This hypothesis was boosted dramatically by Allison Goate's discovery of a defective gene on chromosome 21, which seems to be correlated with the disease and happens to encode for the precursor of beta-amyloid. However, these are discoveries of correlations, not of causes of the disease. There is still no good theory explaining the cause and effect relationships between these proteins, the pathology and the symptoms.

Cures(3, 4) Very few cures seem to be on the horizon. One potential cure that seems to be attracting the most attention is blocking production of beta-amyloid, which many scientists think my actually cause all the other symptoms of AD. Many Biotech firms are working to find a drugs that can block beta-amyloid action, or block production of its precursors. However, these are still far off. There needs to be a better understanding of AD before useful treatments can be developed. No treatments exist to combat the disease itself, but some treatments aim to address the problem in a round about manner. Since many cells killed by AD are acetylcholine secreting, mental processes are effected by a shortage of this neurotransmitter. A drug, Tacrine hydrochloride, blocks the destruction of acetylcholine by enzymes, allowing the brain to get by with a diminished supply. However the drug does not address the more important issues of cell death, brain lesions, plaques, and NFTs. The drug simply temporarily abates the symptoms. Luckily, there are huge research efforts to better understand the disease at a fundamental level, which may eventually lead to more meaningful treatments.

Cause, Pathology and Treatment of Alzheimer's Disease 7.4 of 10 on the basis of 1921 Review.