Chronic inflammation is a feature of many age-related conditions, including neurodegenerative diseases such as Alzheimer's disease. Is inflammation secondary to protein aggregation and other features of aging that drive the development of neurodegenerative conditions, or is inflammation of primary importance in the onset of cognitive impairment and Alzheimer's disease? These are complex conditions in which many forms of pathology and damage interact, and only now are there means to selectively reduce age-related chronic inflammation via the selective destruction of senescent cells. The results of clinical trials of therapies that clear senescent cells should provide some insight into the importance of inflammation in neurogenerative conditions.
Mild cognitive impairment (MCI) is characterized by an abnormal decline in mental and cognitive function compared with normal cognitive aging. It is an underlying condition of Alzheimer's disease (AD), an irreversible neurodegenerative disease. In recent years, neuroinflammation has been investigated as a new leading target that contributes to MCI progression into AD.
In the present study, we assessed a set of various serum and cerebrospinal fluid (CSF) biomarkers, including AD hallmarks and central nervous system and peripheral system inflammatory mediators, in a cohort of 30 healthy control, 45 non-impaired control, and 30 mild cognitively impaired patients. Our results confirmed specific activation of inflammatory processes in the brain of the MCI cohort. Additionally, the presence of systemic biomarkers in the CSF of the MCI population could give an indication of blood-brain barrier (BBB) permeability. Finally, IL-1β was upregulated in MCI serum and correlated with NLRP3 activation biomarkers.
AD has been described as a cascade of several biochemical mechanisms. First, the amyloid plaques start to accumulate abnormally in the brain, triggering an inflammatory response that will chronically exacerbate amyloid deposition and neurotoxicity. This will be followed by the production and hyperphosphorylation of tau proteins generating neurofibrillary tangles. All three mechanisms together are then responsible for altering neuronal transmission in the brain, which results in cognitive decline. Consequently, it is the combination of amyloids, inflammation, and tau proteins together that is responsible for cognitive impairment. As our patients have MCI based on cognitive tests and potentially early AD onset, the stage of the disease could correspond to the transition between amyloid aggregation and inflammatory response activation.