A veteran team of Alzheimer’s disease researchers who have been working in the field for over 30 years proposes that the answer may be yes.
They suggest that if started early enough, a daily regimen of non-prescription non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen can prevent the onset of Alzheimer’s disease (AD).
To identify elevated risk for the development of AD before symptom onset, they propose to use a new non-invasive saliva test, which the team developed and first reported last year.
Their latest research findings are reported in the 2018 - 20th Anniversary celebratory issue of the Journal of Alzheimer’s Disease.
Background
Alzheimer disease is characterized by pathogenic plague deposits of amyloid-β protein in the brain, which become the foci of inflammation. This inflammatory process destroys neurons, leading to cognitive symptoms and clinical onset of Alzheimer’s.
Amyloids are proteins, which become folded into a shape that allows for many copies of it to stick together forming fibrils. Pathogenic amyloids form when previously healthy proteins lose their normal physiological functions and form fibrous plaque deposits around cells. They disrupt the healthy function of tissues and organs, and have been linked to many human diseases.
Lead researcher of the current report is world-renowned Canadian neuroscientist Patrick McGeer, who was the first to discover in 1988 that immune biomarker HLA-DR could be found in the brain. His research team was also the first to report in 1990 that there was significantly fewer AD among rheumatoid arthritis patients who were taking anti-inflammatory drugs.
Studies since then have confirmed the sparing of AD in people taking anti-inflammatory medications, provided that the NSAIDs started at least 6 months, and preferably as early as 5 years before clinical diagnosis of AD typically prevailed.
Research findings and new test
In their latest report of AD research findings, the team suggests
- staging the development and progression of AD
- using a non-invasive test to identify elevated AD risk
- using NSAIDs anti-inflammatory drugs as a preventive measure for those at risk
Staging Alzheimer’s
- AD commences with Aβ deposit in the brain with consequent Aβ levels decrease in the cerebrospinal fluid.
Prevalence of diagnosed AD commences at age 65, and disease onset is supposed to be at least 10 years earlier, at age 55. Without intervention, the prevalence would double every 5 years.
Thus, detecting Aβ levels at stage one is essential. - Biomarker studies suggest that stage 2 sets in about 5 years later. Aβ deposits in the brain can easily be detected by PET scanning. Aβ decreases in cerebrospinal fluid continue. Tau protein aggregation in the brain is also induced.
- Typically in another 5 years, there is slight metabolic decline and reduction in brain tissue uptake of glucose, demonstrated in fluorodeoxyglucose (FDG) – PET brain scan. There may be synaptic loss.
- Mild cognitive impairment is detectable typically in another 5 years. Hippocampal atrophy becomes evident in MRI scanning. Aβ and tau continue to be expressed at the same levels in cerebrospinal fluid.
- Another 5 years, AD can easily be diagnosed clinically. Increasing brain volume loss is evident in MRI, Aβ deposits continue to accumulate in the brain.
- Cognitive deficits progress from mild to severe. Full-time care becomes necessary and therapeutic opportunities are minimal. Yet it is in this stage that most clinical trial have been conducted, researchers pointed out, with 242 of the last 243 AD clinical trials failed.
New saliva test
The team reported last year that they have developed a simple method to determine levels of Aβ42 in tissues and in saliva, and found that the protein is produced in all tissues of the body not just in the brain.
When they analysed the saliva Aβ42 levels of study participants diagnosed with AD and those without AD (non-AD), they found that:
- Results fell into two distinct categories with no overlapping:
- low level (19 - 25 pg/ml range) for most non-AD participants
- high level (41- 60 pg/ml range) for all AD cases, and about 20% of the non-AD participants.
- Lowest level non-AD participants, who were not at risk for AD, secreted levels close to 20 pg/ml regardless of age, sex, or time of day their samples were taken, and their levels remained the same from day to day during the study.
- Researchers suggest non-AD participants with high levels comparable to AD participants' levels are at elevated risk for AD.
Implications
The researchers cautioned that their data is preliminary and need to be confirmed by further research.
If validated, they suggest that the saliva test can be used to identify people at risk for AD years before cognitive symptoms, when there is still a good chance to start anti-inflammatory NSAIDs to ward off Alzheimer’s.
More studies to investigate NSAIDs as a preventive measure for AD - what is the appropriate dose, whether to take it continuously, and when to start taking it – are also needed, they pointed out.
