In Alzheimer’s disease, injuries develop along the axons and dendrites of neurons . These focal injuries cause selective transport abnormalities and nerve cell death. In an Alzheimer’s patient’s brain, the entire brain is degraded resulting in tissue loss. The cortex of the brain shrivels up, which damages the ability of the brain to think, plan, and remember. Alzheimer’s patients go through memory loss problems because of the cortex being wrinkled.
Additionally, Alzheimer’s builds up various kinds of amyloid plaques in the brain which are, dense abnormal clusters of protein found between nerve cells. The plaque usually builds up in the hippocampus region of the brain which aids in the storage of long and short term memory. It has been stated through extensive research that plaques could possibly be one of the reasons behind cell death and tissues loss in Alzheimer’s disease. Interestingly, Apolipoprotein E ε4- a gene found on chromosome 19 is associated with having relevance to the amyloid plaques. Apolipoprotein E ε4 is known to play an important role in lipid transport, cellular metabolism, cell maintenance and repair. However, in the Central Nervous System, apoE2 and E3 (alleles of Apolipoprotein) are more effective in this role than apoE4, and there is some evidence in apoE4 being detrimental in the process of cell transport. One of the possible reasons presented is because it increases the deposition of the beta amyloid plaque in the brain and promotes lysosomal leakage. ApoE4 also aids in dysregulation of tau phosphorylation, disruption of cytoskeletal structure, and mitochondrial damage. ApoE4 disrupts the existing pathology of a neuron. A number of studies have confirmed the negative effect of ApoE4 on the brain but the mechanism behind how it does it, still needs some research and understanding.
Another suspect which is known to lead to cell death and tissue loss are the neurofibrillary tangles which are found in dead nerve cells. These insoluble tangles contain twisted strands of phosphorylated tau proteins and clog the brain. The increasing number of tangles correlate directly with the degree of dementia. The tau proteins play an extremely important role in an AD brain as these proteins are responsible for keeping the microtubules ( which help in communication and transport between neurons) stable. In an AD brain, the chemical make up of the tau protein is changed and the threads of tau become twisted and tangled. This causes the microtubules to become dysfunctional which then causes the neuron transport system to collapse gradually.