Association of Early Beta–amyloid Accumulation and Neuroinflammation Measured with [¹¹C]PBR28 in Elderly Individuals Without Dementia

Objective: To examine whether early β–amyloid (Aβ) accumulation and metabolic risk factors are associated with neuroinflammation in elderly individuals without dementia.

Methods: We examined 54 volunteers (mean age 70.0, 56% women, 51% APOE ε4 carriers) with a TSPO-tracer [¹¹C]PBR28 to assess neuroinflammation and with [¹¹C]Pittsburgh compound B (PiB) to assess cerebral Aβ accumulation. [¹¹C]PBR28 and [¹¹C]PiB standardized uptake value ratios (SUVRs) were quantified in six regions of interests by using the cerebellar cortex as a pseudo-reference/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 Aβ40, Aβ42, total-tau, phospho-tau, soluble TREM2 and YKL-40 levels were measured.

Results: Among the whole study group, no significant association was found between [¹¹C]PiB and [¹¹C]PBR28 SUVR composite scores (slope 0.02, p=0.30). However, higher [¹¹C]PiB binding was associated with higher [¹¹C]PBR28 binding among amyloid negative ([¹¹C]PiB composite score ≤1.5) (TSPO-genotype, age and sex adjusted slope 0.26, p=0.008) but not among amyloid positive participants (slope: -0.004, p=0.88). Higher CSF sTREM2 (r_s 0.72, p=0.01) and YKL-40 (r_s=0.63, p=0.04) concentrations were associated with a higher [¹¹C]PBR28 composite score. Higher body mass index, HOMA-IR, and hs-CRP were associated with higher [¹¹C]PBR28 binding in brain regions where Aβ accumulation is first detected in Alzheimer’s disease (AD).

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.