CAUSES:
Extra-cellular deposition of the amyloid B protein and intracellular aggregation of tau protein (senile plaques and tangles) have been used as post-mortem markers for Alzheimer’s disease. It is not clear if markers actually cause the disease or if they are just the final products of complex events within the brain (Pietrzik & Behl, 2005).
According to some sources, however, the two main pathological frontrunners of Alzheimer’s disease are senile plaques and neurofibrillary tangles. Recent work has established that these pathogenic changes occur in a consistent pattern (Shankle & Amen, 2004).
Accumulation of beta-amyloid plaques: In normal brains, APP, a precursor protein is normal and necessary for brain development and repair. After it is used by the brain for this development and repair, it is broken down into a 37-amino acid fragment. This fragment is then recycled into more APP protein. People stricken with Alzheimer’s disease, have shown to have higher levels of one of two enzymes. These special enzymes, known as the beta and gamma secretases, help in the break down of APP into two different amino acid fragments. Both of these fragments are known as beta amyloid. The special 42-amino acid fragment (BA42) or one of the beta amyloid’s is believed to have a major role in the disease process of Alzheimer’s disease (Shankle & Amen, 2004).
Later, the BA42 amino acid fragments combine with naturally occurring salt and water within the brain which causes these fragments to crisscross with one another creating BA42 complexes. They damage the brain in two very important ways:
1.They invade and convert normal, harmless, naturally-occuring plaques into deadly neuritic plaques. These plaques then disrupt the normal repair process of the brain and causes dysfunction. 2. Secondly, BA42 complexes cause too much calcium to enter post synaptic neurons, which leads to over-excitation. This programs them to turn on the death genes and these neurons commit apoptosis, or neuron suicide (Shankle & Amen, 2004).
Formation of neurofibrillary tangles: Inside the cell themselves, the second primary process occurs. Proteins called tau, are a micro-tubule associated protein that is involved in microtubule assembly and stabilization (Moore & Moore, 2003). Tau’s role is normally to form the neuron’s basic shape and backbone. Mutations on certain chromosomes have been found, which causes the tau protein to twist, interfering with the exit of molecules from the cell body to the outer regions (Goryunov & Liem, 2007). With this buildup of wastes inside the cell, eventually it withers and dies. In the case of Alzheimer’s disease, a significant increase in these tangled filaments accumulates inside the neuron and blocks healthy activity (Shankle & Amen, 2004).
From a total average of 350,000 neurons in young adult controls, a number as low as 72,000 is found in AD patients (Mulligan, Van der Linden, & Juillerat, 2003).
GENETIC FACTORS:
Mutations of the following genes have been described to be causative for Alzheimer’s disease: presenilin-1 gene on chromosome 14, presenilin-2 gene on chromosome 1, and amyloid precursor protein gene on chromosome 21 (Pietrzik & Behl, 2005).
At least four genetic causes of AD are known to increase BA42 production:
1. Inheriting the E4 version of the apolipoprotien E (apoE) gene on chromosome 19, may cause Alzheimer’s disease to appear after age 65;
2. Overproduction of amyloid precursor protein (APP) by the beta APP gene on chromosome 21, causes Alzheimer’s disease to appear early, between age 35 and 65; People with Down syndrome are also affected by this gene.
3. Inheriting the Presenilin 1 gene on chromosome 14, causes Alzheimer’s disease to appear early, between age 35 and 65;
4. Inheriting the Presenilin 2 gene on chromosome 1, causes Alzheimer’s disease to appear early or later, between age 40 and 85 (Shankle & Amen, 2004).
2. The formation of neurofibrillary tangles inside the neurons: The second primary process occurs within the cells themselves. Proteins called tau, normally form the neuron’s basic shape and backbone. Microscopically, they look like steel girders that give the neuron its characteristic shape. Mutations of a gene on chromosome 17 have been found to cause the tau protein to twist, blocking the flow of molecules from the cell body to the outer regions, causing the cell to wither and die. With AD, there is a significant increase in these tangled filaments or neurofibrillary tangles, which accumulate inside the neuron and block healthy activity (Shankle & Amen, 2004).
Environmental Risks could also be seen as risk factors for Alzheimer’s disease. A recent study concluded that alcohol use can increase the risk for heart disease, stroke, vascular dementia, and possibly Alzheimer’s (Shankle & Amen, 2004).