Napping too much might be an early warning sign of Alzheimer’s disease, according to new research.
Brain cells that help keep us awake are the first targeted by the disastrous disease, often causing overwhelmingly sleepiness to the patient during the day.
The cells are destroyed by the spread of toxic clumps of a protein called tau – rather than another known as beta-amyloid.
The finding may lead to earlier diagnosis when drugs and lifestyle changes are more likely to work.
It also could lead to better treatments as well.
“Our work shows definitive evidence that the brain areas promoting wakefulness degenerate due to the accumulation of tau – not amyloid protein – from the very earliest stages of the disease,” said senior author Dr. Lea Grinberg, a neurologist at the University of California, San Francisco (UCSF).
Alzheimer’s damage can take root up to 20 years before clinical symptoms appear. It may be why medications have failed so far because they are given to trial participants too late.
Scientists may also have been aiming at the wrong target – amyloid instead of tau.
Researchers and caregivers recorded regular dozing in patients long before their memory problems started to unfold.
However, it was uncertain whether troubled sleep would put individuals at danger for Alzheimer, or whether changes in the brain associated with the disease would lead to it.
Now the US team has strong evidence to suggest it is the latter by analyzing the brains of deceased patients.
Three areas that boost wakefulness – the locus coeruleus (LC), lateral hypothalamic area (LHA) and tuberomammillary nucleus (TMN) – had lost over 75% of their neurons. They also had a significant build-up of tau.
“It is remarkable because it is not just a single brain nucleus that is degenerating, but the whole wakefulness-promoting network,” said Lead author Dr. Jun Oh, also based at the Memory and Ageing Center at UCSF.
“Crucially this implies that the brain has no way to compensate because at the same moment all these functionally associated kinds of cells are being demolished.”
The study – published in the journal Alzheimer’s and Dementia – demonstrates these regions, including the part affected by chronic sleepiness or narcolepsy, are among the first casualties of neuro-degeneration in sufferers.
So excessive napping – particularly when it occurs in the absence of significant nighttime sleep problems – may serve as an early warning sign of the disease- and the link to tau adds to evidence it contributes more directly to the symptoms than the more extensively investigated amyloid.
The researchers precisely compared the pathology, tau levels, and neuron numbers in 13 people with Alzheimer’s when they died with seven healthy controls.
They also examined samples from seven patients with two distinct forms of dementia caused by tau accumulation called PSP (progressive supranuclear palsy and CBD (corticobasal disease).
In contrast to the Alzheimer’s brains, the wakefulness neurons appeared to be spared despite comparable levels of tau.
“It seems the wakefulness-promoting network is particularly vulnerable in Alzheimer’s disease. Understanding why this is the case is something we need to follow up in future research,” Dr.Oh said.
Increased focus on the role of tau in Alzheimer’s suggests treatments currently under development in the laboratory of Dr. Grinberg and elsewhere that directly address tau have the potential to improve sleep and other early symptoms.
“In addition to holding a key to slowing the progress of the disease overall,” the scientists added.