Obesity associated with Alzheimer's disease
Systemic immunity supports lifelong brain function.
Obesity posits a chronic burden on systemic immunity.
Independently, obesity is a risk factor for Alzheimer's disease (AD).
Here we show that high-fat obesogenic diet accelerated recognition-memory impairment in an AD mouse model (5xFAD).
In obese 5xFAD mice, hippocampal cells displayed only minor diet-related transcriptional changes, whereas the splenic immune landscape exhibited aging-like CD4+ T-cell deregulation.
Following plasma metabolite profiling, we identified free N-acetylneuraminic acid (NANA), the predominant sialic acid, as the metabolite linking recognition-memory impairment to increased splenic immune-suppressive cells in mice. Single-nucleus RNA-sequencing revealed mouse visceral adipose macrophages as a potential source of NANA. In vitro, NANA reduced CD4+ T-cell proliferation, tested in both mouse and human. In vivo, NANA administration to standard diet-fed mice recapitulated high-fat diet effects on CD4+ T cells and accelerated recognition-memory impairment in 5xFAD mice.
The authors suggest that obesity accelerates disease manifestation in a mouse model of AD via systemic immune exhaustion.
Source: Nature Communications