A lay summary written by Mathurra Chandrabose and reviewed Dr Naomi Hartopp, Dr Scott Allen and a Dementia lay panel.
Background
Alzheimer’s Disease (AD) is an ageing-associated disorder that develops over time due to damage to brain cells that can occur naturally with age. It can take many years before individuals show clinical symptoms which can help to identify the problem as AD. Clinical symptoms include memory impairments, changes in personality and behaviour, and a decline in ability in decision-making, planning and performing tasks. Identifying the disease at a late-stage limits treatment options and there is no available cure for AD yet. Thus, being able to identify AD at an earlier stage in people could be beneficial as treatments to slow down the progression of AD can be administered earlier.
There are protector proteins called amyloid and tau in our brain that keep our brain cells healthy. Amyloid is cut into smaller fragments improperly in individuals with AD which leads to the formation of amyloid beta deposits which stick together, forming clumps called amyloid “plaques”. The brain of people with AD has incorrectly modified tau which sticks to other tau proteins, causing “tangles”. The modified tangle, phosphorylated tau (p-tau) and total tau (t-tau) were found to be elevated in individuals with AD.
In summary, the brains of people with AD have a build-up of amyloid beta plaques and neurofibrillary tau tangles. In addition, acetylcholinesterase (AChE),-one of the body’s chemical messengers that play a role in the function of memory, is reduced in AD patients compared to controls. Thus, amyloid beta, p-tau, t-tau and AChE could be used as measurable indicators (biomarkers) that allow the identification of AD. The standard diagnosis for AD consists of brain imaging techniques which are tests that scan our brain in a non-invasive manner and can identify the biomarkers of AD through visual pictures. There are different types such as positron emission tomography (PET) and structural magnetic resonance imaging (MRI) that are used in the diagnosis of AD. However, these techniques are expensive for patients.
Why is the study important?
This study analysed if the levels of p-tau, t-tau, amyloid beta and AChE in salivary samples may be sensitive biomarkers for clinically diagnosing AD. This is important because saliva can be obtained easily so if biomarkers of AD can be found through saliva, this would be helpful in diagnosing AD at an early stage allowing earlier treatment. As brain imaging techniques are expensive, salivary biomarkers could serve as a first step.
What did the authors do and how did they do it?
A meta-analysis is a process of combining the results of multiple studies through statistical analysis to find an overall common pattern. The authors conducted a meta-analysis on 13 studies that obtained data on salivary biomarkers in AD patients versus controls: seven studies on salivary amyloid beta, five studies on salivary t-tau, four studies on salivary p-tau and three studies on AChE. A ratio number was generated for each individual study. The ratios of the amount of each salivary biomarker mentioned were compared between patients and control groups in each study.
What are the results?
AD patients were found to have higher levels of salivary amyloid beta deposits compared to controls. There were no statistical differences in the levels of salivary t-tau, p-tau and AChE between AD patients and controls. This may suggest that the levels present in all saliva samples may be at a low level to make a substantial difference to detect statistical differences.
What do the finding mean going forward for people with the disease?
The findings suggest that salivary amyloid beta levels may be used as a biomarker for identifying AD. However, these differences were not found with other salivary markers. The present study has a low sample size due to the limited number of studies available on salivary biomarkers and AD. Thus, further research could potentially gather supporting evidence to determine whether salivary amyloid beta can be a useful indicator of AD. This means salivary amyloid beta could serve as a quick test for AD. Even though individuals will still need a PET scan for an AD diagnosis, salivary amyloid beta could be used to identify individuals at risk of AD, helping individuals to tackle the disease at an earlier stage. Individuals may have more time to prepare themselves, enter clinical trials at earlier disease stages, and start treatment to slow down the progression of AD at an earlier stage.