Niemann-Pick disease type C (NPC) is a condition you’ve probably never heard of. It’s an extremely rare disease, occurring in approximately 1 in 100,000 live births. But despite its rarity, the strange connections between NPC and a much more common condition, Alzheimer’s disease, are now leading researchers to consider how the connected mechanisms of these two diseases may help us in our search for a cure.

What Is Niemann-Pick Disease?

Children with NPC, including Addison and Cassidy Hempel shown in this article’s top image, typically appear normal until reaching middle to late childhood. Around that age, they begin experiencing subtle symptoms such as clumsiness, poor handwriting, and impaired speech. Some children lose the ability to move their eyes up and down or side to side. These problems gradually worsen over time, with affected children eventually losing the ability to speak or swallow. They may also develop seizures, involuntary muscle contractions, or other movement disorders.

Perhaps even more tragic than the physical symptoms are the effects of NPC on the brain. Children with this condition experience a progressive loss of memory and cognition, which has led to the disease’s unofficial name of “childhood Alzheimer’s disease.” Eventually, after a decline that can last many years, these children succumb due to respiratory failure or severe seizures. There is currently no effective cure or treatment.

The Cholesterol Connection

NPC is caused by a mutation in one of two genes, known as NPC1 and NPC2. These genes are necessary for cells to be able to process and transport cholesterol. While cholesterol is often seen as something to avoid in our diets, we actually require a small amount of it to survive. Our cells need cholesterol to create new membranes or synthesize steroid hormones. When we consume cholesterol, it gets engulfed in cellular compartments called lysosomes, where it is processed and later released into the cell membrane. In people with NPC, cholesterol can’t be properly processed, so it gradually accumulates inside their lysosomes, especially within neurons. With all their cholesterol trapped, the neurons eventually begin to degenerate and die.

NPC is an extreme example of what can happen when cholesterol metabolism goes awry. However, it’s not the only neurological disease that cholesterol plays a role in. People with Alzheimer’s disease, the most common form of dementia, tend to have higher levels of cholesterol in their brains than healthy controls. This may result in increased production of amyloid-beta, a toxic protein that’s considered one of the main causes of Alzheimer’s disease. Interestingly, patients with NPC also show increased levels of amyloid-beta in their cerebrospinal fluid, as well as the accumulation of tau (another toxic protein related to Alzheimer’s disease) inside their brains.

The connections between NPC and Alzheimer’s disease don’t stop there. Studies have found that mutations in NPC1 and other genes involved with cholesterol metabolism lead to an increased risk of Alzheimer’s disease. This suggests that cholesterol could be a key contributor to the neurodegeneration that occurs in both Alzheimer’s disease and NPC.

Where We Go From Here

Rare diseases like NPC are largely ignored by pharmaceutical companies, simply because they aren’t common enough for the research and development of a drug to turn a profit. While each of these diseases by itself is extremely uncommon, because there are thousands of different conditions out there, it’s estimated that 25 million Americans suffer from a rare disease. Most of these have no effective treatment.

Studying rare diseases may not be profitable, but they’re still incredibly important. As previously discussed in a fantastic SciShow video, rare diseases can often provide insight into the causes of more common conditions that share the same underlying mechanism. NPC and Alzheimer’s disease provide just one example of how researching cures for a disease that affects only a few thousand people worldwide could help us to learn about another condition that kills millions every year.

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