The first research on Alzheimer’s disease began as soon as it was discovered and identified by Alois Alzheimer at the beginning of the 1900s. Initially, for several decades, the disease was characterized as pre-senile dementia which was differentiated from that of the older population. Eventually, the two conditions became unified under the name of Alzheimer’s disease. Today, the forms of this disease characterized by the time of onset (late or early) are still studied as separate types. Moreover, in the contemporary world, Alzheimer’s disease has been gaining the attention of doctors, scientists who are currently focusing their effort on the search for a treatment of the disease. To intervene the development of Alzheimer’s disease, its biology and mechanisms are to be studied and understood carefully.
Discovery of Alzheimer’s Disease and the First Findings
During his first research, Alzheimer established that the disease could be associated with amyloid plaques and neurofibrillary tangles based on which, the scientists who studied the disease later admitted the etiology of this illness that they recognized as “organic” (Small & Gandy, 2006). The histological research tendencies typical for the initial decades of the research were soon replaced by molecular and genetic features. Namely, the onset of the shift occurred in 1984 as analyzing the amyloid plaques the scientists identified their core peptide – amyloid β (Aβ) (Small & Gandy, 2006). The identification of the amyloid precursor protein (APP) gave another push to the understanding of the mechanism of the disease.
Genetic Factors and Determinants of Early-Onset Alzheimer’s Disease
Today, the set of the primary hallmarks and key contributors to Alzheimer’s disease includes a range of toxic proteins (such as tau) whose abnormal accumulation leads to the failure of communication between the neurons of the brain resulting in death or permanent damage to the brain cells (NIH, 2014). In addition to these aspects, modern scientists focus on a range of other factors and reactions that are perceived as involved in the process of disease development. Besides, when it comes to the genetic predisposition to Alzheimer’s disease, its occurrence in families has been related to the presence of a mutation in the presenilin gene in the individuals. In other words, the family members who inherit the mutations are more likely to develop an early-onset Alzheimer’s disease. Moreover, the research has pointed out that the subjects with the presenilin mutation tend to produce a much higher level of β-amyloid 42 (20% higher), which is an extremely toxic type of β-amyloid protein (NIH, 2014). Besides, the biology of the people carrying this gene mutation also had a distinct difference in the rates of clearing β-amyloid 42. To be more precise, their cerebrospinal fluid contained a lower level of the toxic protein which made the researchers conclude that it remained in the brain forming amyloid plaques (NIH, 2014).
Research Concerning Late-Onset Alzheimer’s Disease
When it comes to the cognitive decline that occurs in later life, the researchers find it rather difficult to find patterns and provide viable explanations. For instance, there is a series of cognitive decline symptoms that are specifically associated with older age; many of them can be observed in individuals who were not diagnosed with Alzheimer’s disease or any of the known age-related cognitive impairment illnesses. There are no biological explanations for these phenomena (one of such happenings is the abnormal production of DNA-binding protein 43 also known as TDP-43 which is associated with most neurodegenerative processes that occur in later life and are recognized as dementia) (NIH, 2014). That way, compared to the cases of Alzheimer’s disease with early-onset, those that occur later in life 9after the patients turn 65) tend to be much more difficult to study and explain. One of the most commonly identified risk factors of late-onset Alzheimer’s disease is apolipoprotein E ϵ4. Currently, the role of this apolipoprotein is unclear; however, the scientists have noticed that impaired clearance of accumulation of β-amyloid can be detected in the patients who inherit two or even one ApoE ϵ4 alleles (Holmes & Wilkinson, 2000).
Prevention, Treatment, and Possible Ways to Reverse the Pathology
One of the primary and most commonly explored approaches to the prevention of Alzheimer’s disease on the biological level is therapeutic gene transfer, a measure that is rather recent and that existed only in a form of a theory just a couple of decades ago. The studies focusing on the prevention strategies for Alzheimer’s disease with early onset test a theory that β-amyloid antibodies could be used for a purpose to reduce the level of β-amyloid in the patients’ brains preventing the formation of plaques and, therefore delaying or reversing the symptoms (Alzheimer’s Association, 2016). A similar study targeting individual between the ages of 65 and 85 who are under a high risk of developing Alzheimer’s disease are conducted as well. Another approach is based on the reverse of tau pathology which is a factor contributing to the cognitive decline in patients with Alzheimer’s disease. The animal study conducted in Massachusetts involved mice that were given the mutant tau gene; further, with the help of medication, tau pathology was turned on, and soon, mice were observed to develop tau tangles and symptoms of degeneration in neurons (NIH, 2014). After the gene was turned off, the tangles went away, and the cognitive impairments were partially reversed. As a result, the scientists concluded that treating abnormal tau is a way allowing to reverse the symptoms of Alzheimer’s disease it causes even after the damage has occurred (NIH, 2014).
Some other treatment approaches for Alzheimer’s disease are designed to address it at the early stages. Such approaches involve the use of β-amyloid inhibitors that minimize the activity of β- enzymes and γ-secretase in order to increase the cleavage of β-amyloid with APP (Holmes & Wilkinson, 2000). Besides, β-amyloid inhibitors also may be used for the optimization of accumulation and clearance of β-amyloid. Moreover, additional symptomatic treatment strategies target the arrest of the development of Alzheimer’s disease with the help of medications among which there are anti-inflammatory agents (for the minimization of inflammatory processes in the patient’s brain), drugs supporting the neurotransmitters, and antioxidants (to prevent the abnormal accumulation of β-amyloid) (Holmes & Wilkinson, 2000, NIH, 2012).
Alzheimer’s disease is one of the main concerns of the contemporary healthcare. The rates of its prevalence are anticipated to increase with the aging of the Baby Boom generation. Today, the primary practical treatments of Alzheimer’s disease have a symptomatic character and one of the major prevention strategies is a healthy lifestyle (regular physical activity, no smoking or alcohol intake, and a healthy diet). The biology of this disease is rather common and its main sign – cognitive decline, is typical for a range of other known and unexplained conditions many of which are age-related.
References
Alzheimer’s Association. (2016). Prevention and Risk of Alzheimer’s and Dementia.
Holmes, C. & Wilkinson, D. (2000). Molecular biology of Alzheimer’s disease. Advances in Psychiatric Treatment, 6(3) 193-200. Web.
NIH. (2012). Developing New Treatments for Alzheimer’s Disease. Web.
NIH. (2014). Untangling Alzheimer’s Biology. Web.
Small, S. A. & Gandy, S. (2006). Sorting through the Cell Biology of Alzheimer’s Disease: Intracellular Pathways to Pathogenesis. Neuron, 52(1), 15-31.