Alzheimer’s Disease, a type of dementia, affects more than 24 million people worldwide, and its epidemiology can be traced back to as early as 600 CE. The disease is often described as a living death — memories fade to black, the brain fails to retain information, mood swings set in, and appetite dwindles. While a person suffering from Alzheimer’s is living, in real-time, the brain’s hard drive is erasing itself. Since its first documentation, the disease has been widely misunderstood: societies in the Middle Ages perceived Alzheimer’s as a punishment for the patient’s sins. Similar stigmatization of the disease is evident throughout history as seen in “A history of Alzheimer’s.” It describes how patients with Alzheimer’s “were representative victims of a witch hunt that was widespread over the 14th and 15th centuries.” This demonized Alzheimer’s till the 1800s, when research on the disease began. It wasn’t until 1910 that Alzheimer’s Disease received the name the world now recognizes. Through the examination of brains of deceased patients with Alzheimer’s, a German scientist, Alois Alzheimer, made the groundbreaking disocvery that Alzheimer’s directly alters the cerebral cortex. He noted a thinning of the cerebral cortex and the presence of tangles of senile plaques. While these tangles only furthered the mystery that was Alzheimer’s, this was the first time their occurrence was localized to a specific brain region. This conundrum stagnated research on the disease, stumping scientists for years. Dementia and Alzheimer’s are largely unique diseases, and for many years remained the only disorders that could erase a person’s entire existence from memory—that is until 1982, when prion diseases were first recorded. Though it does not induce a senility as severe as Alzheimer’s, the prion has the ability to wreak incurable havoc on the brain. The prion is a misfolded PrPc protein which, on its own, is commonly found throughout the nervous system and is believed to play a role in preventing apoptosis (programmed cell death) in fetal neurons. However, during the process of protein transcription, mutations cause an otherwise healthy protein to misfold, transforming it into a neurotoxic prion that induces a severe cognitive decline, one alarmingly similar to that which ensues in Alzheimer’s. This mutated protein is denoted as PrPSC. Interestingly, with age, the chances of developing this mutation increase, so sporadic onset of a kind of prion disease is possible. Similarly, Alzheimer’s can be sporadic and affect older age groups. Where the two disorders differ is in their pre-transcription phases. Alzheimer’s has been connected back to the amyloid protein precursor (APP), a gene which is located on the 21st chromosome. This gene was first discovered during a study of down-syndrome (DS) patients aged 30 and 40 who developed symptoms of dementia. Because individuals with DS have two copies of chromosome 21, they are more likely to develop the isoform (one of various proteins that could be translated from mRNA strands during transcription) responsible for Alzheimer’s. The result of the production of these isoforms is what Alois Alzheimer himself discovered: the buildup of amyloid-beta plaque in the brain. However, the presence of the plaque itself is not always an indicator of the disease, so there is a piece of the puzzle between the time of transcription and translation that researchers are missing. The amyloid-beta molecule can take on various forms, among which are the Aβ-40 and Aβ-42 peptides. Of the two, Aβ-42 is believed to be the neuro-lethal form of the molecule, distinguishing itself as the clearest link between APP and the presentation of Alzheimer’s. This link is referred to as the amyloid cascade hypothesis. While this hypothesis still receives some criticism from within the research community, it is the most widely investigated hypothesis regarding Alzheimer’s. While prions have been able to provide more insight into the disorder, prions are less pathologically advanced than the disease itself. The mystery surrounding Alzheimer’s Disease has to undergo more investigation before a clear cause is pinpointed. According to the Journal “Emerging Topics in Life Sciences,” scientists have been able to diminish the infectivity of the scrapie, a prion disease typical in cattle, by treating animal subjects’ brains with, “chemicals that modify or hydrolyze protein,” essentially breaking down the toxic PrPSC. Meanwhile, attempts to reduce the amyloid-beta plaque build up in the neuron pathways of Alzheimer’s patients has proven to be unsuccessful in preventing cognitive decline. It is often thought to be a question of timing; finding the disease in its earlier stages may provide more success in treatment. Future hope for treatments lie in research regarding the prevention of Aβ-42 translation within brain cells.
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