For other diseases, the syndromes are hard to classify because of the variants that can only be separated by genotyping after the mutant genes had taken into affect. Some disorders display errors in DNA replication, where there is an increased number of trinucleotide repeats or by a cellular loss of function. The abnormalities are caused by malformation in transport, degradation and aggregation of proteins that lead to cell specific changes and neuron death.
Alzheimer's disease is a form of dementia that occurs in elderly people. As people advance in their age and life expectancies increases, the risk of developing the disease also increases. Two major types of changes occur in the brains of people with Alzheimer's disease. The first is the formation of neurofibrillary tangles, in which the cellular material within the cell bodies of neurons becomes replaced with densely packed, twisted microtubular proteins called tau, which is hyperphosphorylated. The second change is the development of senile neuritic plaques, which are clusters of dead or dying neurons mixed with the protein, tau. It is not known whether senile plaques or neurofibrillary tangles come first. Several illnesses are characterized by dementia and are associated with selective loss and atrophy of neurons found in the frontal and temporal lobes of the brain. It is found that frontotemporal dementia, such as Prick's disease is associated with mutations in tau.
Studies done on understanding the pathogenesis of Alzheimer's disease report that several genes have been identified with patients. Beta-amyloid-42 has been linked with families with familiar early onset of the disease. Seven different mutations in the gene for the amyloid precursor protein has been found to increase the making of beta amyloid 1- 42, leading to fibrillar aggregation toxic to neurons. A second locus linked early onset cases has been found on chromosome 14q and encodes a presenilin 1.
