Normal aging, motor neurone disease, and Alzheimer’s disease are characterized by cortical changes in inflammatory cytokines

Abstract

The role of increased brain inflammation in the development of neurodegenerative diseases is unclear. Here, we have compared cytokine changes in normal aging, motor neurone disease (MND), and Alzheimer's disease (AD). After an initial analysis, six candidate cytokines, interleukin (IL)-4, 5, 6, 10, macrophage inhibitory protein (MIP)-1α, and fibroblast growth factor (FGF)-2, showing greatest changes were assayed in postmortem frozen human superior frontal gyri (n = 12) of AD patients, aging and young adult controls along with the precentral gyrus (n = 12) of MND patients. Healthy aging was associated with decreased anti-inflammatory IL-10 and FGF-2 levels. AD prefrontal cortex was associated with increased levels of IL-4, IL-5, and FGF-2, with the largest increase seen for FGF-2. Notwithstanding differences in the specific frontal lobe gyrus sampled, MND patients' primary motor cortex (precentral gyrus) was associated with increased levels of IL-5, IL-6, IL-10, and FGF-2 compared to the aging prefrontal cortex (superior frontal gyrus). Immunocytochemistry showed that FGF-2 is expressed in neurons, astrocytes, and microglia in normal aging prefrontal cortex, AD prefrontal cortex, and MND motor cortex. We report that healthy aging and agerelated neurodegenerative diseases have different cortical inflammatory signatures that are characterized by increased levels of anti-inflammatory cytokines and call into question the view that increased inflammation underlies the development of agerelated neurodegenerative diseases.

Case report: Evolution of catatonic mutism and psychotic symptoms in an adolescent with Down syndrome: transition from Down syndrome disintegrative disorder to anti-N-methyl-D-aspartate receptor encephalitis

“…Amyloid plaques in DS can be detected on neuropathology as early as 8-9 years of age when there are no signs of dementia. From this perspective, it is intriguing that IL-5, IL-15, PDGFbb, and VEGF were found to be raised in the CSF of the current patient, all of which are upregulated in AD brains, but not in NMDARE in general (19)(20)(21)(22). These findings support the concept that pre-AD disease contributes to the evolution of DSDD (3).…”

Effects of Qi-Fu-Yin on aging of APP/PS1 transgenic mice by regulating the intestinal microbiome

“…In ELISA experiments (Yang et al, 2011), TNF-a and IL-6 in the brain tissue and serum of APP/PS1 transgenic mice were found to be elevated at 9 months of age compared with wild-type mice, and the differences were significant at 12 months of age and even more significant at 18 months of age. Compared to normal aging patients, concentrations of IL-5 were significantly higher in the superior frontal gyrus of patients with AD, followed by no significant difference in IL-6 (Tennakoon et al, 2022). In contrast, there were no significant differences in IL-5, IL-6, TNF-a in the plasma of tau P301S transgenic mice after 11 months of age (Sun et al, 2020).…”

Integrated Multi-Omics Analysis of Brain Aging in Female Nonhuman Primates Reveals Altered Signaling Pathways Relevant to Age-Related Disorders

“…Also noteworthy is that previous human studies of molecular changes in PFC with age have reported changes related to inflammation and immune function (Zhang and Wong 2022;Tennakoon et al, 2022;Wruck and Adjaye 2020), and reported evidence of age associated differences in immune function in PFC. However, the analyzed tissue samples were derived from seven studies with high heterogeneity in patient populations, cause of death, and PMI.…”