Alzheimer's (ADEOA) Disease Analysis

Autosomal dominant mutations in APP, PSEN1, or PSEN2 that alter APP processing and the production or self aggregation of Aβ, promote aggregation and accumulation of Aβ in brain causing early-onset AD (Bertram et al., 2010).

Familial Alzheimer’s Disease (FAD) is a form of mental deterioration characterized by the formation of amyloid plaques around neurons in the brain. While there appears to be multiple ways general Alzheimer’s Disease (AD) can develop, FAD is a rare type of AD that can be acquired hereditarily. Of all general Alzheimer’s cases, around 1-5% are FAD specific, which translates to about 50,000 to 250,000 people (Strobel). Children of people who have acquired certain genetic mutations linked with FAD have been shown the potential of inheriting these mutations and developing FAD as a result. Mutations in the presenilin proteins (PSEN1; PSEN2) or in the amyloid precursor protein (APP) have been shown to be linked with FAD. PSEN1 is most prominently

Alzheimer's is an adult onset disease that is caused by a genetic mutation in chromosomes 21, 14, and 1. Alzheimer’s is a complex series of brain changes that occur over a long period of time. It is a progressive disease that destroys memory and other important mental functions, this disease is the most common form of dementia; it is irreversible and scientist have not found a cure for it.

Alzheimer’s disease is named after Dr. Alois Alzheimer who first discovered deviations from normal tissues of healthy individuals in the brain tissue of a lady in 1906. The woman, who showed symptoms of erratic behavior, loss of memory, and problems with communication, died of a then unfamiliar mental disorder. This led Dr. Alzheimer to investigate the cause of her unusual death. He assessed the brain of the woman and found that there were many anomalous masses (amyloid plaques) and intertwined bundles of fiber (neurofibrillary tangles). Scientists today have pinpointed the qualities of Alzheimer’s to be a) tangles in the brain (neurofibrillary tangles), b) plaque in the brain (amyloid plaques), and c) loss of connections among nerve cells.

On November 25th, 1901, Alois Alzheimer, an assistant physician at the psychiatric institution in Frankfurt, examined fifty-one year old, Auguste D.. During the evaluation, Alzheimer observed strange behaviors in Auguste. She exhibited a series of symptoms that included problems with memory and comprehension, an inability to speak, disorientation, hallucinations, and behavioral issues. Five years later on April 8th, 1906, Auguste died and Alzheimer, who worked at the Royal Psychiatric Clinic, performed an autopsy using her brain. Alzheimer discovered two unusual pathologies. First, lodged in between nerve cells, were massive amounts of sticky, insoluble proteins. Second, within the neurons themselves, there were tangled bundles of protein

The genetic variant increases the disease risk but is not a direct cause however. Inheritance change is linked to at least one of the three genes that were discussed above. It affects members of at least two generations and makes up 1% of Alzheimer cases. Most people that have Down syndrome develop Alzheimer’s because they have the extra chromosome 21. Deterministic genes are a direct cause of the disease, those who inherit deterministic genes will likely develop a disorder. Inheritance of the gene may appear in a new family if not it is a 50/50 chance. For example, a child whose mother or father carries a genetic mutation for eFAD has a 50/50 chance of inheriting the mutation. If the mutation is inherited, the child will have a strong possibility of developing eFAD. Most cases of eFAD are inherited and other cases the disease is developed without any specific known cause.

These plaques are made out of nerve cells surrounded by dying neurons. The same beta amyloid is a splice from a larger protein called amyloid precursor protein (Qué es la enfermedad de Alzheimer?, n.d., para. 5).

The causes of Alzheimer’s disease are still for the most part unknown. Scientists can’t quite pinpoint the exact causes of Alzheimer’s. But for the last twenty years the cause getting the most attention is that it is caused by an excess amount of insoluble fragments of beta-amyloid, then that leads to the loss of connection between brain cells, then eventually the death of said brain cells. (American Scientist, 44)

There is a large supply of amyloid plaques in the cells of people with Alzheimer’s disease. Amyloid plaques are clustered pieces of protein that build up between nerve cells. They speed up the production of beta amyloid, which are polypeptides of about thirty-six to forty-three amino acids long (emedicinehealth, 2014; Stanford Medicine, 2013). Amyloid precursor proteins (APP), when split into specific pieces, are producers of beta amyloid. They are found in tissues and organs, such as the brain. Amyloid precursor proteins pass through a fatty membrane on the outside of a cell. This allows them to extend from the

The strongest genetic risk factor for late onset AD is APOE, a locus that is found on chromosome 19. (Corder, 1993) APOE can be found as three different alleles (APOE-2/3/4), but APOE-3 is the most common allele, as it occurs in 72% of the population. (Karch, 2014) While early onset AD mutations in APP lead to an altered production of Aβ isoforms in the brain, APOE influences Aβ by affecting its aggregation and clearance process. APOE-4 binds to Aβ much more rapidly than other APOE alleles, which accelerates fibril formation and increases the odds of neurofibrillary tangles; furthermore, APOE also regulates Aβ metabolism. The combination of these facets allows APOE to influence the amount and structure of intraparenchymal Aβ deposits.

Early-Onset occurs in people around the mid 40’s to early 50’s range, according to the National Institute on Aging (NIA). NIA also states that Early-Onset is the result of a genetic mutation. With that, it is found that suffers of Down Syndrome are more likely to develop Alzheimer’s because “the extra chromosome they have contains the gene that produces harmful amyloid” (NIA). The amyloid can be seen as an imposter, presenting itself to deceive the body of the truth. It poses as an “inherited form of Alzheimer’s,” Alz.org suggests, therefore tricking the body (Alz). Along with the non-visual characteristics, one can actually see a physical difference, but not where one might expect. If you look at a person with Alzheimer’s you may not be able to tell they have the disease unless you engage in a conversation, but if you look at the brain of an Alzheimer’s suffer there is a clear, physical difference when compared to a healthy brain. The brain that has developed Alzheimer’s will appear to have pieces missing and be smaller in size. This reason is because Alzheimer’s targets parts of the brain causing them to decay and after time the brain just starts to shrink. The disease actually begins in the hippocampus which is the part responsible for memory and continues from there (NIA). Consequently, Alzheimer’s is known as the memory loss

“Alzheimer’s disease is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills, and eventually the ability to carry out the simplest tasks individuals with AD may start having symptoms their mid-60s” (nih.gov). AD is a multifactorial and progressive neurodegenerative disease. “Parts of AD, for example, increased oxidative state, amyloid plaque deposition, and neurofibrillary tangle of tau protein in the central cortex the limbic system of the brain, have been related with Alzheimer 's disease. The disease was once thought to be a natural part of aging; it is an extremely incapacitating type of mental dementia. Albeit, some dementia

No one particular gene has been found to be responsible for this disease. Researchers have been able to find genes and alleles that may increase the risks for developing Alzheimer’s. Often time’s early onset Alzheimer’s disease is caused by a mutation on a chromosome.

Nevertheless, both types of AD are recognised pathologically by the build-up of intracellular neurofibrillary tangles, extracellular amyloid plaques, and massive neuronal and synaptic loss (Carmo & Cuello, 2013). Neurofibrillary tangles are aggregates of hyper-phosphorylated tau protein and plaques are mostly insoluble deposits of β-amyloid, resulting from the cutting of the amyloid precursor protein (APP) (Farooqui & Farooqui, 2011). The discovery of mutations in the APP gene which cause familial AD lead to the articulation of the amyloid cascade hypothesis (ACH) (Hardy & Asllop, 1991). A large amount of evidence supports this view; however a number of findings are contrary to its proposal. As a result, Armstrong (2011) proposed a revision of the hypothesis, postulating that the main trigger for the development of the disease is the ageing of the brain and related wear and tear such as head trauma and stress; collectively referred to as the “allostatic load” (Carroll, 2002). Furthermore, a greater emphasis has now been placed on the role of small, soluble amyloid oligomers which seem to be the cause of early cell dysfunction in AD, rather than the large, insoluble amyloid fibrils. (Ferreira, Vieira & De Felice, 2007).

Dementia includes many diseases, and Alzheimer’s disease (AD) is the most common (Schultz-Krohn, Foti, & Glogoski, 2012). The cause of AD is not well understood. Individuals with AD have characteristic neurofibrillary tangles and beta-amyloid plaques that cause neuronal loss and the shrinking of overall brain structure (Atchison & Dirette, 2012). Significant loss of neurons occur in the cerebral cortex impacting thinking, judgment, reasoning, speech, and language (Atchison & Dirette, 2012). AD can be classified as early onset, before the age of 65, or more commonly late onset, after the age of 65 (Atchison & Dirette, 2012). Gene mutations are typically seen in AD, but do not cause the late onset form of AD; however, three genes are responsible for causing the early onset form of AD (Atchison & Dirette, 2012). Although age is the strongest risk factor, having Down syndrome is a genetic risk factor for developing AD (Atchison & Dirette, 2012). Researchers estimate 13% of adults over the age of 65 have AD, and women have a higher incidence of AD (Schultz-Krohn et al., 2012; Atchison & Dirette, 2012).