Most mutations in the APP and presenilin genes increase the production of a small protein called amyloid beta (Aβ)42, which is the main component of amyloid plaques. Some of the mutations merely alter the ratio between Aβ42 and the other major forms—particularly Aβ40—without increasing Aβ42 levels. Two other genes associated with autosomal dominant Alzheimers disease are ABCA7 and SORL1.Most cases of Alzheimers are not inherited and are termed sporadic Alzheimers disease, in which environmental and genetic differences may act as risk factors. Most cases of sporadic Alzheimers disease in contrast to familial Alzheimers disease are late-onset Alzheimers disease (LOAD) developing after the age of 65 years. Less than 5% of sporadic Alzheimers disease have an earlier onset. The strongest genetic risk factor for sporadic Alzheimers disease is APOEε4. APOEε4 is one of four alleles of apolipoprotein E (APOE). APOE plays a major role in lipid-binding proteins in lipoprotein particles and the epsilon4 allele disrupts this function. Between 40 and 80% of people with Alzheimers disease possess at least one APOEε4 allele. The APOEε4 allele increases the risk of the disease by three times in heterozygotes and by 15 times in homozygotes. Like many human diseases, environmental effects and genetic modifiers result in incomplete penetrance.
An example of this situation would be an individual who has a fear of mice but lives in an area without mice. Even though the concept of mice causes marked distress and impairment within the individual, because the individual does not usually encounter mice, no actual distress or impairment is ever experienced. It is recommended that proximity to, and ability to escape from, the stimulus also be considered. As the phobic person approaches a feared stimulus, anxiety levels increase, and the degree to which the person perceives they might escape from the stimulus affects the intensity of fear in instances such as riding an elevator (e.g. anxiety increases at the midway point between floors and decreases when the floor is reached and the doors open). The DSM-V has been updated to reflect that an individual may have changed their daily activities around the feared stimulus in such a way that they may avoid it altogether. The person may still meet criteria for the diagnosis if they continue to avoid or refuse to participate in activities they would involve possible exposure to the phobic stimulus. Specific phobias
A specific phobia is a marked and persistent fear of an object or situation. Specific phobias may also include fear of losing control, panicking, and fainting from an encounter with the phobia. Specific phobias are defined concerning objects or situations, whereas social phobias emphasize social fear and the evaluations that might accompany them. The DSM breaks specific phobias into five subtypes: animal, natural environment, blood-injection-injury, situational and other.