Sleep deprivation accelerates Alzheimer's brain damage

Sunday, 27 Jan, 2019

'We don't know yet whether getting adequate sleep as people age will protect against Alzheimer's disease. The test is already commercially available; it detects NfL in cerebrospinal fluid for measurement of different neurological conditions, and Jucker is confident that future clinical trials for new Alzheimer's drugs will include the marker his team developed.

However, James Pickett, head of research at the UK Alzheimer's Society, said that "in research we've supported to uncover the key risk factors for Alzheimer's disease, gum disease hasn't emerged as a major cause for concern".

Alzheimer's disease is the most common form of dementia, which is characterized by memory loss that gets worse over time. In more than 90% of the more than 50 Alzheimer's brain samples, they also spotted toxic enzymes produced by the bacteria called gingipains. The scientists then tested the brains of 53 people with Alzheimer's disease, finding the toxic enzymes from P.?gingivalis in 51 of them.

"I think I've found a bacterial cause of Alzheimer's", Dominy, who co-founded Cortexyme with Lynch and now serves as the company's Chief Scientific Officer, told her. Dominy had spent about 15 years searching for infections that might lead to Alzheimer's until evidence for a bacterium known as P. gingivalis became "undeniable", according to Lynch. Over six weeks, they established infections in the mouths of otherwise healthy mice and indeed discovered the presence of the bacterium in their brains.

Aricept, Exolon, Razadyne, Namenda and Namzaric are all treatments that just address some symptoms in some people, and do not treat an underlying cause of the disease. Her team previously found that P. gingivalis actively invades the brains of mice with gum infections.

"We have not only identified the epigenetic factors that contribute to the memory loss, but we also found ways to temporarily reverse them in an animal model of Alzheimer's", said Zhen Yan, Professor at University at Buffalo in the US. The authors said further study of neuropsychological deficits associated with AD in elderly Hispanic patients, and consideration of possible health disparities and cultural adaptation of cognitive tests, is necessary. The drug cleared the infection from the animals' brains and reduced β-amyloid production and neurodegeneration.

Writing in the journal, the scientists concluded: "The findings of this study offer evidence that P. gingivalis and gingipains in the brain play a central role in the pathogenesis (development) of AD (Alzheimer's disease), providing a new conceptual framework for disease treatment".

There was also caution about the fact the drug tests had been in mice.

The findings, which were published in the January 14 issue of Nature Medicine, can potentially help with early Alzheimer's diagnoses and new drug development.

Of the many changes in the brain which precede the disease's symptoms, one change is also the accumulation of NfL in the blood before any symptoms begin, said Jucker.

Much the same effect was seen in people.

"The evidence we found is important to moving forward because early identification of Alzheimer's disease can allow for earlier implementation of treatments and interventions that prolong the life and well-being of patients and their caregivers", said first author Gali Weissberger, PhD, a postdoctoral researcher at USC Keck School of Medicine.

But, alternatively, it may be that people with Alzheimer's have poorer oral hygiene, perhaps because the condition makes them less able to look after their teeth and gums.