Fig. 4: Within the brain (represented by the circle) a neuron that has developed a tangle sends out 2 processes. One makes a synaptic contact, which is endangered as the tangle decreases the neuron's capacity to tend its branches. Another process is engulfed in an extracellular amyloid deposit, forming part of a senile plaque; an inflammatory cell (microglia) is in the vicinity. Factors influencing the development of AD appear outside the brain. The determinant genes influence the production of amyloid peptide, and the susceptibility gene (ApoE) is involved in the aggregation of amyloid and growth and repair functions of neurons. Age-related oxidative damage to neuronal membranes and proteins is enhanced by amyloid and inflammation; iron may participate in this process. Head trauma increases the development of plaques and tangles, whereas the mechanisms by which infarcts increase the risk for dementia in patients with AD lesions are unknown. Estrogen has multiple effects on the brain, several of which may influence the development of dementia.