Insomnia Can Be an Early Alzheimer’s Warning Sign. New Research Explains Why. : ScienceAlert

Problems with sleep often show up much earlier than more recognizable symptoms in people who develop Alzheimer’s disease, but why? A new study offers a major clue, tied to the toxic build-up of tau protein in the brain that accompanies Alzheimer’s.

These tau tangles are known to damage brain cells and disrupt communications between them, leading to some of the cognition and memory issues typically associated with Alzheimer’s disease.

The researchers behind the new study, led by a team from the University of Kentucky in the US, have discovered something else: tau can essentially ‘hijack’ the brain’s energy supply, keeping neurons overexcited and making it harder for the brain to drift off to sleep.

Using tau-related disease models in mice, the researchers showed that when tau builds up abnormally, the brain doesn’t use sugar to make energy in the normal way, but instead produces glutamate, a neurotransmitter that stimulates neurons and helps us learn and remember.

Like tau, glutamate is usually beneficial, but too much of it keeps the brain on high alert – and that makes it hard to fall asleep. One possibility is that it’s something of an emergency response by the brain to keep running, as tau begins to cause disruption.

“It’s like a petulant toddler who just won’t calm down and go to sleep,” says principal investigator Shannon Macauley, a physiologist from the University of Kentucky.

“The brain is hijacking all your glucose to make glutamate over and over again, keeping the system awake and preventing it from reaching the deep, restorative stages of sleep necessary for recovery and memory formation.”

Significantly, the researchers noticed this hijacking at the early stages of tau starting to malfunction, even before it had started clumping in full. This may explain how poor sleep can often precede Alzheimer’s by many years – though it’s also worth remembering that this research only looked at the brains of mice.

Past research has linked Alzheimer’s disease to problems with the chemical channels that produce energy in brain cells. One of the prevailing theories around the condition is that issues with these channels correctly reading blood sugar levels – and responding to them – can contribute to Alzheimer’s progression.

Here, the researchers suggest that the tau protein tangles are involved in sending the brain’s energy supply into overdrive, rerouting the ‘fuel’ and throwing out the balance between excitation and inhibition.

There’s a cyclical process going on here: Alzheimer’s can disrupt sleep, which then also worsens the disease. But recognizing this cycle could help scientists break it.

The researchers suggest that existing medication that modifies the brain’s metabolism, such as drugs for epilepsy or type 2 diabetes, could quieten the hyperactivity and help patients sleep better. That in turn could slow progression of the disease.

“What’s really exciting is that it seems some of these phenotypes are reversible,” says Macauley. “That means you don’t have to grow back neurons or get rid of all the plaques and tangles in your brain to rescue sleep.”

The study is also further evidence of the complexity of Alzheimer’s when it comes to its causes and consequences.

It’s likely that any effective Alzheimer’s treatment is going to have to tackle multiple processes that have gone awry in the brain – and quite possibly elsewhere in the body too, as the disease has repeatedly been linked to inflammation in the gut, for example.

Related: Blood Test ‘Clock’ Can Predict Alzheimer’s Symptoms Before They Emerge

In the meantime, there is an increasing number of Alzheimer’s risk factors that we know about, and many of them are connected to lifestyle choices.

“Until there are more disease-modifying treatments, it is critical to highlight factors, like sleep, that individuals can modify to reduce vulnerability,” says physiologist Riley Irmen, from the University of Kentucky.

“Connecting these basic science findings to meaningful public impact is especially important for the community.”

The research has been published in npj Dementia.