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

Sini Toppala, Laura L. Ekblad, Jouni Tuisku, Semi Helin, Jarkko J. Johansson, Hanna Laine, Eliisa Löyttyniemi, P. ivi Marjamäki, Kaj Blennow, Henrik Zetterberg, Antti Jula, Matti Viitanen, Juha O. Rinne

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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 years, 56% women, 51% APOE ɛ4 carriers) with the translocator protein (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 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 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 (slope -0.004, p = 0.88) participants. Higher CSF soluble TREM2 (rs = 0.72, p = 0.01) and YKL-40 (rs = 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 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.
Original languageEnglish
Pages (from-to)e1608-e1619
JournalNeurology
Volume96
Issue number12
DOIs
Publication statusPublished - 23 Mar 2021
Externally publishedYes

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