Association of Early β-Amyloid Accumulation and Neuroinflammation Measured With [11C] PBR28 in Elderly Individuals Without Dementia

Objective To examine whether early beta-amyloid (A beta) accumulation and metabolic risk factors are associated with neuroinflammation in elderly individuals without dementia. Methods We examined 54 volunteers (mean age 70.0 years, 56% women, 51% APOE epsilon 4 carriers) with the translocator protein (TSPO) tracer [C-11]PBR28 to assess neuroinflammation and with [C-11] Pittsburgh compound B (PiB) to assess cerebral A beta accumulation. [C-11]PBR28 and [C-11]PiB standardized uptake value ratios (SUVRs) were quantified in 6 regions of interests by using the cerebellar cortex as a pseudo-reference and reference region, respectively. Fasting venous glucose, insulin, and high-sensitivity C-reactive protein (hs-CRP) values were determined. Homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. A subset of individuals (n = 11) underwent CSF sampling, and A beta 40, A beta 42, total tau, phospho-tau, soluble TREM2, and YKL-40 levels were measured. Results Among the whole study group, no significant association was found between [C-11]PiB and [C-11] PBR28 SUVR composite scores (slope 0.02, p = 0.30). However, higher [C-11]PiB binding was associated with higher [C-11]PBR28 binding among amyloid-negative ([C-11]PiB composite score <= 1.5) (TSPO genotype-, age- and sex-adjusted slope 0.26, p = 0.008) but not among amyloid-positive (slope -0.004, p = 0.88) participants. Higher CSF soluble TREM2 (r(s) = 0.72, p = 0.01) and YKL-40 (r(s) = 0.63, p = 0.04) concentrations were associated with a higher [C-11]PBR28 composite score. Higher body mass index, HOMA-IR, and hs-CRP were associated with higher [C-11]PBR28 binding in brain regions where A beta accumulation is first detected in Alzheimer disease. Conclusions While there was no association between amyloid and neuroinflammation in the overall study group, neuroinflammation was associated with amyloid among the subgroup at early stages of amyloid pathology.

Automated summary

While there was no association between amyloid and neuroinflammation in the overall study group, neuroinflammation was associated with amyloid among the subgroup at early stages of amyloid pathology. Higher body mass index, HOMA-IR, and hs-CRP were associated with higher neuroinflammation in brain regions where A beta accumulation is first detected in Alzheimer disease.