From the Turku PET Centre (S.T., L.L.E., J.T., S.H., J.J., P.M., J.O.R.) and Department of Biostatistics (E.L.), University of Turku; Kuopio City Home Care (S.T.), Rehabilitation and Medical Services for Elderly, Kuopio, Finland; Amsterdam Alzheimer Center (L.L.E.), Amsterdam UMC, the Netherlands; Department of Radiation Sciences (J.J.), Umeå University, Sweden; City of Turku (H.L.), Welfare Division, Turku City Hospital, Turku, Finland; Department of Medicine (H.L.), University of Turku, Turku University Hospital, Finland; Department of Psychiatry and Neurochemistry (K.B., H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square; UK Dementia Research Institute at UCL (H.Z.), London; National Institute for Health and Welfare (A.J.); Department of Geriatrics (M.V.), Turku City Hospital; University of Turku (M.V.), Finland; Division of Clinical Geriatrics (M.V.), NVS, Karolinska Institutet, Stockholm, Sweden; and Division of Clinical Neurosciences (J.O.R.), Turku University Hospital, Finland.
Neurology. 2021 Mar 23;96(12):e1608-e1619. doi: 10.1212/WNL.0000000000011612. Epub 2021 Jan 29.
To examine whether early β-amyloid (Aβ) accumulation and metabolic risk factors are associated with neuroinflammation in elderly individuals without dementia.
We examined 54 volunteers (mean age 70.0 years, 56% women, 51% ɛ4 carriers) with the translocator protein (TSPO) tracer [C]PBR28 to assess neuroinflammation and with [C] Pittsburgh compound B (PiB) to assess cerebral Aβ accumulation. [C]PBR28 and [C]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 Aβ, Aβ, total tau, phospho-tau, soluble TREM2, and YKL-40 levels were measured.
Among the whole study group, no significant association was found between [C]PiB and [C]PBR28 SUVR composite scores (slope 0.02, = 0.30). However, higher [C]PiB binding was associated with higher [C]PBR28 binding among amyloid-negative ([C]PiB composite score ≤1.5) (TSPO genotype-, age- and sex-adjusted slope 0.26, = 0.008) but not among amyloid-positive (slope -0.004, = 0.88) participants. Higher CSF soluble TREM2 ( = 0.72, = 0.01) and YKL-40 ( = 0.63, = 0.04) concentrations were associated with a higher [C]PBR28 composite score. Higher body mass index, HOMA-IR, and hs-CRP were associated with higher [C]PBR28 binding in brain regions where Aβ accumulation is first detected in Alzheimer disease.
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.
探讨无痴呆症的老年人群中，早期β-淀粉样蛋白（Aβ）积累和代谢危险因素是否与神经炎症有关。
我们检查了 54 名志愿者（平均年龄 70.0 岁，56%为女性，51%为 ɛ4 携带者），使用 translocator 蛋白（TSPO）示踪剂 [C]PBR28 评估神经炎症，并用 [C]匹兹堡化合物 B（PiB）评估脑内 Aβ 积累。通过使用小脑皮层作为伪参考和参考区，分别对 6 个感兴趣区域的 [C]PBR28 和 [C]PiB 标准化摄取值比（SUVR）进行量化。测定空腹静脉血糖、胰岛素和高敏 C 反应蛋白（hs-CRP）值。计算胰岛素抵抗的稳态模型评估（HOMA-IR）。一部分人（n=11）进行了 CSF 取样，并测量了 Aβ、Aβ、总 tau、磷酸化 tau、可溶性 TREM2 和 YKL-40 水平。
在整个研究组中，[C]PiB 与 [C]PBR28 SUVR 综合评分之间没有发现显著相关性（斜率 0.02， = 0.30）。然而，在淀粉样阴性（[C]PiB 复合评分≤1.5）的个体中，较高的 [C]PiB 结合与较高的 [C]PBR28 结合相关（TSPO 基因型、年龄和性别调整后的斜率为 0.26， = 0.008），但在淀粉样阳性（斜率-0.004， = 0.88）参与者中没有。更高的 CSF 可溶性 TREM2（ = 0.72， = 0.01）和 YKL-40（ = 0.63， = 0.04）浓度与 [C]PBR28 综合评分较高有关。较高的体重指数、HOMA-IR 和 hs-CRP 与在阿尔茨海默病中首先检测到 Aβ 积累的脑区中更高的 [C]PBR28 结合有关。
虽然在整个研究组中，淀粉样蛋白和神经炎症之间没有关联，但在淀粉样蛋白病理早期的亚组中，神经炎症与淀粉样蛋白有关。
