Metabolic Danger Components Related to Neuroinflammation in Key Areas of the Mind Related to AD

Neuroinflammation may be associated with early stages of β-amyloid (Aβ) pathology of the brain, 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 the first An Aβ accumulation is detected in patients with Alzheimer’s disease (AD) according to study results published in Neurology.

This study included 54 volunteers (mean age 70 years; women 56%), about half of whom were APOE ε4 carriers. Study researchers used [11C]Pittsburgh Compound B (PiB) for assessing cerebral Aβ accumulation and TSPO tracer [11C]PBR28 for the assessment of neuroinflammation. You quantified [11C]PBR28 and [11C]PiB standardized admission ratios [SUVR] in 6 regions of interest with the cerebellar cortex as the pseudo reference / reference region.

In addition, the study researchers measured the fasting glucose, insulin and highly sensitive C-reactive protein (hs-CRP) levels of the participants. 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 = 0.30) but the results showed an association between higher ones [11C]PiB binding and higher [11C]PBR28 binding in amyloid negative participants (P = 0.008) compared to amyloid positive participants (P = 0.88).

In addition, study researchers found that a higher [11C]The composite PBR28 score was associated with both higher sTREM2 (P = 0.01) and YKL-40 (P = 0.04) concentrations of cerebrospinal fluid. They also found significant associations between higher levels [11C]PBR28 binding in regions where Aβ accumulation is first detected in AD and higher BMI (parietal cortex: P = 0.002; precuneus: P = 0.03) and homeostatic model assessment of insulin resistance (P = 0.005).

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

Based on their results, the researchers concluded that “the association between metabolic risk factors and clinically diagnosed AD observed in epidemiological studies can be at least partially mediated by neuroinflammation”.

reference

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