Behind the Brain

Alzheimer’s (also known as AD) is a neurodegenerative disease that results in memory loss and is responsible for 60% of dementia cases. 10.5% of people aged 65+ have Alzheimer’s. Although the cause is relatively unknown, there are several symptoms that we can look out for to identify symptoms.

Symptoms of Alzheimer’s:

There are three different categories of Alzheimer’s symptoms. Before a diagnosis is made, any symptom is referred to as a initial symptom. Once a diagnosis of Alzheimer’s is made, symptoms are classified under one of two categories: Early Stage Symptoms, Middle Stage Symptoms, and Late Stage Symptoms.

Initial Symptoms: Alzheimer’s symptoms can start as early as 8 years before the initial diagnosis. These initial symptoms include an inability to learn, an inability to remember recent events, and an inability to do tasks such as managing finances, raising children, or cooking meals. These symptoms are all caused by Mild Cognitive Impairment (MCI). MCI is quite broad, but the MCI topic that is most correlated with Alzheimer’s is Amnesiac MCI. Amnesiac MCI is known as an early indicator of Alzheimer’s and is also a transitional phase between normal aging and dementia.

Early Stage: Patients still in the early stage have one of two types of symptoms. A small number of patients have symptoms related to motor control, such as difficulty in apraxia (executive movements), agnosia (perception), and language. However, the vast majority of patients struggle with memory loss. Typically Alzheimer’s affects memory and learning of patients. But, in the early stage of Alzheimer’s, three types of memories normally are relatively unaffected:

• Implicit Memories: These are related to muscle memory and habitual instincts.
• Episodic Memories: These are memories of events in the patient’s life of when they were younger.
• Semantic Memories:  These are already learnt facts.

Middle Stage: Symptoms in this stage involve the worsening of the loss of memory. Loss of memory can become so bad that the patient forgets their loved ones’ faces. Longe-term memory also is impacted by the memory loss. Furthermore, patients become unable to coordinate different motor sequences, thus increasing the risk of falling. Reading and writing skills also quickly deteriorate, while as patients forget vocabulary, they use incorrect word substitutions, (paraphasia) making their speech inaccurate.

Late Stage: The late stage of Alzheimer’s involves a complete dependence on caretakers. Patients often die due to other medical complications, and are bedridden till death. Often, patients will have paradoxical lucidity, which is when a patient has a sudden mental clarity before death.

Causes of Alzheimer’s

The true cause of Alzheimer’s, like several factors related to the Alzheimer’s disease, is unknown. However, there are some theories and hypothesis. Here are the two most common and popular hypotheses.

• The Amyloid- Beta Hypothesis: Alzheimer’s is caused by an accumulation of the amyloid-beta protein (Aβ). This protein can build up in the form of amyloid plaques, tau proteins, and neurofibrillary tangles. Amyloid plaques are big deposits of the tau protein, typically found in grey matter (depicted by the yellow blobs in the image above). Amyloid plaques are also associated with an abundance of astrocytes and microglia. Tau proteins are a protein that is found in neurons of the CNS. When hyperphosphorylated, Tau proteins make structures within the neuron called a neurofibrillary tangle. A neurofibrillary tangle is a “insoluble aggregate of the tau protein”. Basically this just means, that a neurofibrillary tangle is a disorderly, clump of misfolded tau proteins, which also are insoluble.
• The Cholinergic Hypothesis: Alzheimer’s is caused by the decrease in production of the neurotransmitter, acetylcholine. This hypothesis, along with being the oldest hypothesis of the cause of Alzheimer’s is also what most Alzheimer’s drugs are based off of.
• Genetic Risk Factor Analysis: Scientists look at APOEε4 to determine the risk of the patient getting late-onset Alzheimer’s. APOE plays a role in lipid binding, but the ε4 prevents APOE from lipid binding, thus preventing it from breaking down large amyloid-beta deposits. So by analyzing how many alleles of APOEε4 a patient has, we can determine the risk he gets Alzheimer’s

Potential Cures

Once again, just like Alzheimer’s itself, the cure for Alzheimer’s is unknown. However there have been several discoveries regarding potential treatments for Alzheimers.

• Repurposing Cancer Drugs: Hyperphosphorylation is one of the key mechanisms used for mitosis. When done incorrectly, it can result in cancer. Thus several cancer drugs try to inhibit hyperphosphorylation in cancerous cells, to prevent the cancerous cell from duplicating/ doing mitosis. Now hyperphosphorylation in tau proteins can lead to Alzheimer’s, so by using these same cancerous cells to inhibit hyperphosphorylation, we can theoretically reverse/slow the effects of Alzheimer’s. E.G. of a repurposed drug: Bexarotene.
• Ultrasound: Focused ultrasound has been found to open the blood-brain barrier. Several current Alzheimer’s drugs are unable to cross this barrier, thus unable to deliver maximal impact. By combining ultrasound and these preexisting drugs, we can maximize on Alzheimer’s treatments.
• Antibodies: Antibodies designed to break down amyloid-beta deposits are often used as Alzheimer’s treatments. When combined with ultrasound, studies have shown that they can be much more effective.