Alzheimer disease

Dementia isn’t technically a disease, but more of a way to describe a set of symptoms like poor memory and difficulty learning new information, which can make it really hard to function independently.

Usually dementia’s caused by some sort of damage to the cells in the brain, which can be caused by a variety of diseases. Alzheimer’s disease, now referred to as Alzheimer disease, is the most common cause of dementia.

Alzheimer disease is considered a neurodegenerative disease, meaning it causes the degeneration, or loss, of neurons in the brain, particularly in the cortex. This, as you might expect, leads to the symptoms characteristic of dementia.

Although the cause of Alzheimer disease isn’t completely understood, two major players that are often cited in its progression are plaques and tangles.

Alright, so here we’ve got the cell membrane of a neuron in the brain. In the membrane, you’ve got this molecule called amyloid precursor protein, or APP, one end of this guy’s in the cell, and the other end’s outside the cell. It’s thought that this guy helps the neuron grow and repair itself after an injury.

Since APP’s a protein, just like other proteins, it gets used and over time it gets broken down and recycled.

Normally, it gets chopped up by an enzyme called alpha secretase and it’s buddy, gamma secretase.

This chopped up peptide is soluble and goes away, and everything’s all good.

If another enzyme, beta secretase, teams up with gamma secretase instead, then we’ve got a problem, and this leftover fragment isn’t soluble, and creates a monomer called amyloid beta.

These monomers tend to be chemically “sticky”, and bond together just outside the neurons, and form what are called beta-amyloid plaques—these clumps of lots of these monomers.

These plaques can potentially get between the neurons, which can get in the way of neuron-to-neuron signaling.

If the brain cells can’t signal and relay information, then brain functions like memory can be seriously impaired.

It’s also thought that these plaques can start up an immune response and cause inflammation which might damage surrounding neurons.

Amyloid plaque can also deposit around blood vessels in the brain, called amyloid angiopathy, which weakens the walls of the blood vessels and increases the risk of hemorrhage, or rupture and blood loss.

Here’s an image of amyloid plaque on histology, these clumps are buildups of beta amyloid, and this is happening outside the cell.

Another big part of alzheimer disease though, are tangles, and these are actually found inside the cell, as opposed to the beta-amyloid plaques.

Just like other cells, neurons are held together by their cytoskeleton, which is partly made up of microtubules, these track-like structures that essentially act like a minecart shipping nutrients and molecules along the length of the cell.