Alzheimer's disease, like many age-related conditions, has a strong inflammatory component. Short-term inflammation is a necessary part of the immune response to pathogens and injury. When it goes unresolved, however and is sustained for the long term, it is highly disruptive of cell and tissue function. Aged tissues are characterized by damage and the presence of senescent cells, both of which provoke the immune system into a state of constant inflammatory activation. Researchers here analyze data from older individuals to show that while everyone has a progression towards ever greater chronic inflammation, Alzheimer's disease patients are further along in this process than their healthier peers.
In the present study, we measured 73 inflammatory proteins in both cerebrospinal fluid (CSF) and plasma in a large clinical cohort in order to investigate inflammatory pathway changes in Alzheimer's disease (AD). Our finding that both CSF and plasma proteins were highly predictive of age in amyloid-β negative, cognitively unimpaired individuals (Aβ- CU) individuals adds to the established evidence that the innate immune system changes even during healthy aging. From this basis, we showed that the AD continuum is characterized by accelerated biological aging of the innate immune system such that mild cognitive impairment (MCI) and AD patients have inflammatory proteomes which are akin to healthy individuals who are significantly older. This finding is in line with similar biological aging studies of AD carried out using structural brain imaging (i.e. brain age), for example.
Importantly, the abnormal inflammatory aging we observed in the AD continuum is differentially expressed across specific inflammatory pathways and can even differ depending on whether proteins are measured in CSF or plasma. For instance, our results showing that plasma-based inflammatory aging was elevated in AD patients compared to amyloid-β negative (Aβ-) MCI patients suggest that cross-sectional inflammatory levels as measured in plasma may be more AD-specific at a given point in time compared to those measured in CSF. Since CSF-based inflammatory aging correlated strongly with core AD biomarkers and predicted chronological age better than plasma in the main Aβ- CU group, CSF inflammatory proteins likely track more closely with those brain-based inflammatory changes which occur during normal aging.