MedicineScience & Tech

The Great Big Alzheimer’s Puzzle

Millions of people worldwide suffer from Alzheimer’s disease. My great-grandmother had it, my friend’s grandfather has it. Chances are you know someone who has Alzheimer’s.

The disease is typically characterised by its most common symptom: memory loss. As the brain deteriorates, Alzheimer’s patients have increased difficulty with forming new memories and remembering details about themselves and those they are closest to.

The Great Big Alzheimer's Puzzle

Image Source: Ellen Kuwana

However, a recent study shows that memory loss in Alzheimer’s patients could be reversed. This is one of the many scientific breakthroughs leading to a cure. Scientists have discovered that in patients with Alzheimer’s, there can be several different anomalies occurring in the brain all at once, all of which worsen the state of the disease. New research from the Massachusetts Institute of Technology (MIT) is revolutionary, but it simply helps us understand only one aspect of the ever-changing problem that is Alzheimer’s disease.

The researchers at MIT discovered a way to block an enzyme responsible for memory loss in Alzheimer’s patients, called Histone deacetylase 2 (HDAC2). 

The brain of someone with Alzheimer’s contains elevated levels of HDAC2. This enzyme then binds with a gene called Sp3. This toxic enzyme-gene combination of HDAC2 and Sp3 forms a blockade that compresses the brain’s memory genes so tightly that they can no longer be expressed, resulting in the loss of one’s memory.

The Great Big Alzheimer's Puzzle

Through countless studies, scientists found that reducing HDAC2 levels without affecting other enzymes in the Histone deacetylase (HDAC) family was impossible. Attempts at blocking the HDAC2 enzyme resulted in a drop in HDAC1, resulting in drastically reduced white blood cell production.

Recently, the researchers at MIT decided to take a different approach. Instead of targeting the enzyme HDAC2, they decided to examine the effects of modifying Sp3, the gene that it binds to.

While studying mice with memory loss, scientists discovered that completely deactivating the Sp3 gene restored the mice’s ability to form long-term memories. The scientists isolated the fragment of the HDAC2 enzyme responsible for binding to the Sp3 genes. By replicating this fragment, they were able to have it bind to all the existing Sp3 genes and have them extracted, thus preventing the dangerous HDAC2-Sp3 combination from forming.

As revolutionary as this new treatment is, it is not enough to truly cure Alzheimer’s. As aforementioned, there are several other aberrations of the brain related to Alzheimer’s disease, a couple of which are beta-amyloid plaques and tau protein tangles.

The Great Big Alzheimer's Puzzle

Amyloid plaques and neurofibrillary tangles. (Image Source: Bright Focus)

Beta-amyloid (Aβ) is a protein that accumulates and forms plaques that are toxic to brain cells when they occur in excess. Patients with Alzheimer’s have very high levels of beta-amyloid in their brains and thus exhibit brain tissue degeneration.

Along with several other proteins, beta-amyloid is circulated out of the brain and into the circulatory system by our cerebrospinal fluid during deep sleep. Scientists coined this nocturnal cleaning system the “glymphatic system”, a combination of “glial cells” (a type of brain cell that surrounds a neuron) and the lymphatic system. This discovery has furthered both the research towards a cure for Alzheimer’s disease as well as an increased understanding of the importance of sleep in relation to brain health.

So far, most Alzheimer’s disease research has focused on beta-amyloid, and yet its normal function is still not well understood. Recently, some promising results have arisen from studies on another protein: tau.

Normally, tau ensures that the brain’s transport system is functioning perfectly and that each neuron completes its task correctly. However, if tau collapses inside of dying brain cells to form “tangles”, the brain’s transport system essentially begins to disintegrate, which can cause numerous neurodegenerative diseases, including Alzheimer’s.

The Great Big Alzheimer's Puzzle

As you can see, the many effects of Alzheimer’s disease are caused by combinations and malfunctions of completely different enzymes, genes, and proteins; after solving one problem, there is always another waiting to be solved. Every scientific breakthrough is really just one small piece of a giant puzzle. We know that memory loss reversal works on mice, but now the question is: how do we create an effective and safe treatment for humans? Plus, there are even more treatments that must be developed to address the proteins associated with Alzheimer’s, beta-amyloid and tau.

My extensive research has prompted me to think about the future of a cure for Alzheimer’s and the possible solutions we have yet to discover. Could there be a way to induce cerebrospinal fluid circulation to clear the brain of beta-amyloid plaques? Could there ever be a way to restore damaged brain cells? Could brain tissue transplants ever work as a cure for Alzheimer’s?

All these questions lead me to one conclusion (and a lot more research that I won’t get into here): we still have a lot of work to do in terms of a cure for Alzheimer’s disease, but given all of the research done and advancements made so far, there is hope that the next generation of medical professionals will be the ones to solve the great big Alzheimer’s puzzle.

Hero image: Daniel Contreras

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The Great Big Alzheimer's Puzzle
I should write more often.