Most patients with Alzheimer’s disease feel drowsy and lethargic, but why do they feel so?

A new study has shown that many Alzheimer’s patients experience fatigue due to the degeneration of a type of neuron that keeps us awake, according to Science Daily.

The study, published appears in the April 4, 2022 issue of JAMA Neurology, has also confirmed that the tau protein causes neurodegeneration in those patients.

The data came from patients at UC San Francisco’s Memory and Aging Center who volunteered to have their sleep monitored with an electroencephalogram (EEG) and donate their brains after their death.

Dr. Lea Grinberg, a neuropathologist, and Dr. Thomas Neylan, the study’s senior author, said, “We were able to prove what our previous research had been pointing to — that in Alzheimer’s patients who need to nap all the time, the disease has damaged the neurons that keep them awake.”

“It’s not that these patients are tired during the day because they didn’t sleep at night,” Dr. Grinberg added. “It’s that the system in their brain that would keep them awake is gone.”

The opposite phenomenon occurs in those with other neurodegenerative conditions, like progressive supranuclear palsy (PSP), who also participated in the study. Patients with PSP have damage to the neurons that make them feel lethargic so they become sleep deprived.

Joseph Oh, a medical student and one of the lead authors, said, “You can think of this system as a switch with wake-promoting neurons and sleep-promoting neurons, each tied to neurons controlling circadian rhythms. Finally, with this post-mortem tissue, we’ve been able to confirm that this switch, which is known to exist in model animals, also exists in humans and governs our sleep and awake cycles.”

Oh said these neurons as “extremely smart” as they are able to produce an array of neurotransmitters (brain chemicals) and can excite, inhibit, and modulate other nerve cells.

He said, “It’s a small number of neurons but their computational capabilities are incredible. When these cells are affected by disease, it can have a huge effect on sleep.”

The researchers looked at the brains of 33 Alzheimer’s patients, 20 PSP patients, and 32 participants who had healthy brains before death. They measured the amounts of two characteristic proteins associated with the neurodegenerative process – beta-amyloid and tau.

The team explained that during sleep, the brain clears out the beta-amyloid that accumulates during the day. So, when you cannot sleep, it builds up. Dr. Neylan said that since PSP patients never sleep so he expects to see lots of that protein in their brains. He said, “But it turns out that they have none. These findings confirm with direct evidence that tau is a critical driver of sleep disturbances.”