Uncovering Neural Pathways to Alzheimer’s Disease

Sabrina Singh
7 min readJan 26, 2020

We know a lot about the human body, how it works, why it works in current ways, and how to help treat injuries and diseases. However, we don’t know much about the brain, the organ that controls all of the other organs in the human body.

The brain serves as the center of the nervous system, controlling vital functions including breathing, movement, and heartbeat.

The human brain alone contains roughly 100 billion neurons, thats equivalent to the amount of stars in the galaxy. All of these neurons send electrical and chemical impulses necessary for transmitting information.

So, how do we get a better understanding of these neurons and the pathways they’ve created? This is where connectomics comes in.

Breaking Down Connectomics

Connectomics is essentially the study of connectomes. Connectomes are complete maps of the neural connections in the brain. Our brain has a 100 trillion neural connections! That’s 1000x the number of stars in the galaxy.

Neural Plasticity

Neural connections are the connections that occur when neurons transmit information. The human brain is known to have neural plasticity. This means that the connections in the brain are constantly changing.

Neural plasticity occurs as neurons respond to their external environment. Neurons function as a part of circuit in the body and each neuron can change its functional role by altering how it responds to influences from other neurons. During this time the brain deletes neural connections that aren’t necessary and strengthening the useful ons.

This means your brain is constantly changing! Even after reading this article your brain will change because of neural plasticity.

Developments in Connectomics

These wiring diagrams have a goal of mapping the molecular connections between neurons. Except, we’re not very far into the process. Currently, we only have a complete connectome of the roundworm C. elegans. This animal is a free-living, transparent nematode which only has 300 neurons and 7000 synaptic connections.

Roundworm C. Elegans

The Scientists are also working on developing synaptomes, which are essentially maps that describe the anatomical distribution of different synaptic types.

Scientists are currently looking into developing functional connectomes. These connections are large-scale maps of communicational activity between different brain regions and networks.

Why do we need connectomics?

The purpose of these connectomes is to better under the organization of neural interactions in the brain and attempt to relate brain structures to their functions to understand what parts give us certain abilities.

Developing the human connectome will help shed light on anatomical and functional connectivity within the healthy human brain. This is extremely important because all of our data right now comes from epileptic patients.

The development of the human connectome will allow scientists to produce data sets to facilitate research into neurological disorders and diseases such as dyslexia, autism, and Alzheimer's.

The Human Connectome Project

The Human Connectome Project (HCP) is a group of projects by researchers aiming to understand the major brain pathways, compare essential circuits, zoom into specific regions, and understand the functions of the brain in depth. The Human Connectome Project is essentially the Human Genome Project, but for the brain.

“Historically, we focused on mapping brain structure, but we haven’t spent a lot of time looking at how those structures are wired together, what the connections between them are, and how they function.”

The HCP aims to collect behavioural measures of motor, sensory, cognitive and emotional behaviour. These can be used to better understand a core set of functions relevant to understanding the brain and our behaviour.

HCP is used task-fMRI (tfMRI) to understand the relationships between individual differences in the neurobiological pathways of mental processing in both functional and structural connectivity. TfMRI uses non-invasive techniques including strong magnetic fields and radio waves to establish detailed images of the body.

The Human Connectome Project

The project traces the main neural pathways the link the roughly 500 major regions in the brain. These are then produced in colour to understand how biological circuitry systems in the brain have underlying impacts on our mental functions.

Mapping the human brain

These connections are mapped through the use of electron microscopes. These electron microscopes spend months collecting millions of slices of a specific region of the brain, which are nanometers thick. Then, they’re assembled into a 3-D structure using specific software.

This was done at the Allen Institute for Brain Science in Seattle, who mapped the neural connections of a mouse brain. Five electron microscopes continuously ran for five months and collected over 100 million images of 25,000 slices of the mouse’s visual cortex. Each slice was 40 nanometers thick. By the end of their research, they collected 1.8 petabytes of data (that’s equivalent to 24 years of HD footage). Then, the institute developed a software program to assemble the images into a 3D volume and created a connectome.

Wiring Diagram of Mouse Brain

Researchers hope to use the HCP data to explore how a person’s brain connectivity relates to their mental abilities, including essential functions such as memory, self-control, and decision making. This data can help develop improved treatment for mental disorders.

The use of connectomics can help better develop treatments and understand the root cause of many disorders, one specifically being Alzheimer’s disease.

Understanding Alzheimer’s Disease

Alzheimer's disease (AD) is a neurodegenerative disorder resulting in accumulative neuron death. AD currently affects 500,000 people in the geriatric population in Canada.

Alzheimer's is associated with molecular and cellular changes in the brain. AD is associated with various neuronal changes, including the following.

  1. Excessive amount of amyloid plaques.

In the brain, beta-amyloid is a type of protein which is a breakdown of the amyloid precursor protein. Beta-amyloid plays a major role in the brain for neuronal growth and repair. Patients with AD suffer from abnormal levels of the protein which tend to occur in clumps. These clumps form plaques that collect between neurons and disrupt brain function.

2. Neurofibrillary tangles.

These tangles are of abnormal accumulations of the tau protein found inside neurons. In healthy neurons, tau is used to help normalize and bind to stabilize microtubules, which are resposnbile for intercellular transport of nutrients. In AD, tau proteins bind together and create tangles which block neuron transport harming synaptic communication between neurotransmitters.

3. Buildup of glial cells, specifically microglia.

Glial cells are meant to keep the brain free of debris, and destroy waste or toxins. In the brain of an AD patient, the microglial cells fail to do so. This results in chronic inflammation.

4. Formation of vascular conditions.

Beta-amyloid deposits in the brain arteries may cause vascular issues are they reduce blood flow and oxygen to the brain. This reduction can result in the breakdown of the blood-brain-barrier. Inflammation also adds to vascular problems.

Through AD, the patient’s neurons breakdown and are injured. The final stages of AD include brain atrophy, which causes a significant loss in brain volume due to cell death.

Affects of Alzheimer’s

Patients with Alzheimer’s disease tend to lose many of their essential functions. Including, loss of memory, reduced motor function, loss of cognitive ability, and the ability to perform daily tasks.

AD is known to stem from various genetic, lifestyle, and environmental circumstances. Unfortunately, it takes months for neuropsychological tests and brain scans to diagnose Alzheimer’s, as it can only be definitely diagnosed after death. AD also has no cure. Scientists are looking to identify the underlying causes of Alzheimer’s in the brain to help develop effective treatments.

Functional Connectomes and Alzheimer’s

Through the use of functional connectomics and different imaging modalities including sMRI, diffusion MRI, EEG, and fMRI, researchers have discovered abnormal connectivity in the AD brain.

The brain is essentially made up of grey and white matter. AD had shown decreased interregional correlations of coritcal thickness between the bilateral postcentral gyri and between the bilateral superior parietal lobes. These gyri (folds in the brain) are associated with a persons main sensory receptive area.

Increased correlations were discovered within regions such as the medial prefrontal cortex, the cingulate regions, the supramarginal gyrus, the superior temporal gyrus, and the inferior temporal gyrus. These are gyri which are mainly associated with memory along with the processing of language.

There were no significant variations found between white matter in healthy versus AD controls.

Functional MRI was used to capture blood–oxygen level signals and describe the brain activity. Increases were found in the functional connectivity within the frontal cortices, which decreased activity within the temporal, parietal, and occipital lobes, all associated with major functions in the body.

Also, a decreased correlation was seen between the hippocampus which is necessary for developing the human memory. People with AD generally tend to have a 21% decrease in the volume of their hippocampus.

The Future of Connectomics

Connectomics is continuing to make major advancements. Google has recently rendered a high-resolution connectome of the fly brain.

Rapid advancements in brain imaging have resulted studies worldwide on the connections in the human brain, revealing essential principles in functional systems and fiber connections.

With connectomics and the use of functional connectomes, we’ll soon be able to better understand the underlying fundamentals of Alzheimer’s and the direct correlation between its cause and certain areas of functionality in the brain.

Key Takeaways

  • Connectomes are complete maps of the neural connections in the brain.
  • We only have a complete connectome of the roundworm C. elegans.
  • Developing the human connectome will help shed light on anatomical and functional connectivity within the healthy human brain, to produce data sets which can be used to facilitate research into neurological disorders.
  • The Human Connectome Project aims to understand the major brain pathways, compare essential circuits, zoom into specific regions, and understand the functions of the brain in depth.
  • Alzheimer’s disease is associated with an excessive amount of amyloid plaques, neurofibrillary tangles, buildup of micorglia, and the formation of vascular conditions.
  • Brain imaging and functional connectomics has been used to discover abnormal connectivity in the AD brain.