Metabolic Risk Factors Linked to Neuroinflammation in Key Brain Regions Associated With AD

Neuroinflammation may be associated with early stages of brain β-amyloid (Aβ) pathology, and metabolic risk factors such as high body mass index (BMI) and insulin resistance are strongly associated with neuroinflammation in regions of the brain where Aβ accumulation is first detected in patients with Alzheimer disease (AD), according to study findings published in Neurology.

This study included 54 volunteers (mean age, 70 years; women, 56%), approximately half of whom were APOE ε4 carriers. Study researchers used [¹¹C]Pittsburgh compound B (PiB) to assess cerebral Aβ accumulation and TSPO-tracer [¹¹C]PBR28 to assess neuroinflammation. They quantified [¹¹C]PBR28 and [¹¹C]PiB standardized uptake value ratios [SUVR] in 6 regions of interest with the cerebellar cortex as a pseudo-reference/reference region.

Additionally, the study researchers measured participants’ fasting glucose, insulin, and high sensitivity C-reactive protein (hs-CRP) levels. A total of 29 patients were amyloid-negative (PiB SUVR ≤1.5) and 25 patients were amyloid-positive (PiB SUVR >1.5).

Overall, there was no association between [¹¹C]PBR28 and [¹¹C]PiB SUVR composite scores (P =.30), but the results indicated an association between higher [¹¹C]PiB binding and higher [¹¹C]PBR28 binding in amyloid-negative participants (P =.008) compared with amyloid-positive participants (P =.88).

Additionally, study researchers found that a higher [¹¹C]PBR28 composite score was associated with both higher cerebrospinal fluid sTREM2 (P =.01) and YKL-40 (P =.04) concentrations. They also found significant associations between higher [¹¹C]PBR28 binding in regions where Aβ accumulation is first detected in AD and higher BMI (parietal cortex: P =.002; precuneus: P =.03) and homeostatic model assessment of insulin resistance (P =.005).

A possible limitation of this study included its lack of arterial blood sampling data for some patients and lack of a true reference region in the brain for [¹¹C]PBR28 imaging.

Based on their findings, the study researchers concluded that “that the association between metabolic risk factors and clinically diagnosed AD seen in epidemiological studies could be mediated at least partly through neuroinflammation.”

Reference

Toppala S, Ekblad LL, Tuisku J, et al. Association of early beta-amyloid accumulation and neuroinflammation measured with [11C]PBR28 in elderly individuals without dementia. Published online January 29, 2021. Neurology. doi:10.1212/WNL.0000000000011612