A BRIEF BREAKDOWN: THE DISCOVERY OF ALZHEIMER'S.
In 1901, the first patient diagnosed with Alzheimer's was a woman named Auguste Deter.
Alois Alzheimer, the doctor who diagnosed Auguste, made no progress towards a cure.
Auguste shortly passed away in 1906.
If Auguste had instead been alive today, modern medicine could help her no more than Alois.
However, through epigenetic processes, this disease can be prevented.
What is
Epigenetics?
Epigenetics is the study of changes in organisms caused by modification of gene expression, rather than altercation of the gene code itself. This term includes any process that alters gene activity without altering any DNA sequence. Many epigenetic processes have been identified such as methylation, acetylation, phosphorylation, and the best-known process: DNA methylation.
DNA methylation occurs by adding a methyl (CH3) group to DNA. By adding a methyl group, this changes how specific genes are expressed. In DNA methylation, methyl groups are most typically added at the 5 carbon of the cytosine ring, resulting in 5-methylcytosine, also known as the "fifth base" of DNA. In somatic cells, CpG sites- in which a cytosine nucleotide is located next to a guanine nucleotide, are heavily methylated while CpG islands- sites of CpG clusters, are unmethylated. This allows for gene expression to occur. When a CpG island is methylated, the gene is then no longer expressed and turned off.
The addition of methyl groups to DNA is controlled and carried out by a family of enzymes called DNA methyltransferases (or DNMTs): DNMT1, DNMT3a, and DNMT3b. DNMT1 is responsible for the maintenance of established DNA methylation patterns. DNMT3a and DNMT3b are responsible for the mediation of newly established DNA methylation patterns.
DNA Demethlyation
DNA demethylation is the remove of a methyl group from DNA and is as equally important to epigenetic processes as DNA methylation. The demethylation process is vital to the reprogramming of genes and key to tumor progression. There are two types of DNA methylation: active and passive.
Active DNA methylation mainly occurs by removing 5-methylcytosine through the sequential modification of cytosine bases that have been converted by ten-elevation translation (TET)-mediated oxidation. the TET family of 5-mC hydroxylases promote DNA demethylation by binding to regions that are rich in CpG to prevent unwanted DNA methyltransferase activity.
Passive DNA methylation takes place on newly synthesized DNA strands through DNMT1 during replication.
What is
ALzheimer's?
Alzheimer's disease is an irreversible, progressive brain disorder that impairs proper cognitive abilities. A majority of the people who are affected are older adults, typically 60+ years of age. Being the most common cause of dementia, this disease accounts for 60-80% of all dementia cases. Common symptoms include, but are not limited to: memory loss, severe behavioral changes and or mood swings, hallucination, paranoia, loss of appetite, and the inability to control voluntary bladder and bowel functions. There are essentially 7 Stages of Alzheimer's Disease that can indicate the presence of this disorder in a person.
AD pathogenesis is believed to be triggered by the accumulation of the amyloid beta peptide, which is due to overproduction of amyloid beta and/or the failure of clearance mechanisms. Amyloid beta self-aggregates into oligomers, which can be of various sizes and forms, diffuse and neuritic plaques in the parenchyma and blood vessels. Amyloid beta oligomers and plaques are potent synaptic toxins, block proteasome function, inhibit mitochondrial activity, alter and stimulate inflammatory processes. Loss of the normal physiological functions of the protein is also thought to contribute to neuronal dysfunction. It interacts with the signaling pathways that regulate the phosphorylation of the microtubule-associated protein TAU. Hyperphosphorylation of TAU disrupts its normal function in regulating axonal transport and leads to the accumulation of neurofibrillary tangles and toxic species of soluble tau. Furthermore, degradation of hyperphosphorylated tau by the proteasome is inhibited by the actions of amyloid beta. These two proteins and their associated signaling pathways, therefore, represent important therapeutic targets for AD.
While there are no cures or a current way to slow the progression of AD, there are medications for behavioral and memory changes.
Memory
The U.S. Food & Drug Administration (FDA) has approved of two types of medications: cholinesterase inhibitors and memantine to treat cognitive symptoms.
Cholinesterase Inhibitors: commonly prescribed for mild to moderate AD
-prevents the breakdown of acetylcholine, a chemical messenger that supports communication among nerve cells when in high concentrations.
Memamine: commonly prescribed for moderate to severe AD
-regulates the activity of glutamine, a chemical involved in information processing
Behavioral
The U.S. Food & Drug Administration (FDA) has approved of two types of medications: cholinesterase inhibitors and memantine to treat cognitive symptoms.
Antidepressants: for low mood and irritability
Anxiolytics: for anxiety, restlessness, verbally disruptive behavior/resistance
Antipsychotics: for hallucination, delusion, aggression, agitation, hostility, etc.
*increased risk in stroke/death; should only be used if:
-behavioral symptoms due to mania/psychosis
-symptoms present are dangerous to the patient and or others
- the patient is experiencing inconsolable or persistent distress or a significant decline in function
