Douglas Mental Health University Institute, Montréal, Québec, Canada.
Centre for the Studies in the Prevention of Alzheimer's Disease, Montréal, Québec, Canada.
Alzheimers Dement. 2022 May;18(5):875-887. doi: 10.1002/alz.12442. Epub 2021 Sep 29.
We examine the role of brain apolipoprotein B (apoB) as a putative marker of early tau pathology and cognitive decline.
Cerebrospinal fluid (CSF) samples from cognitively normal and Alzheimer's disease (AD) participants were collected to measure protein levels of apoB and AD biomarkers amyloid beta (Aβ), t-tau and p-tau, as well as synaptic markers GAP43, SYNAPTOTAGMIN-1, synaptosome associated protein 25 (SNAP-25), and NEUROGRANIN. CSF apoB levels were contrasted with positron emission tomography (PET) scan measures of Aβ (18F-NAV4694) and Tau (flortaucipir) along with cognitive assessment alterations over 6 to 8 years.
CSF apoB levels were elevated in AD participants and correlated with t-tau, p-tau, and the four synaptic markers in pre-symptomatic individuals. In the latter, CSF apoB levels correlated with PET flortaucipir-binding in entorhinal, parahippocampal, and fusiform regions. Baseline CSF apoB levels were associated with longitudinal visuospatial cognitive decline.
CSF apoB markedly associates with early tau dysregulation in asymptomatic subjects and identifies at-risk individuals predisposed to develop visuospatial cognitive decline over time.
我们研究了脑载脂蛋白 B（apoB）作为早期 tau 病理和认知能力下降的潜在标志物的作用。
从认知正常和阿尔茨海默病（AD）参与者中收集脑脊液（CSF）样本，以测量 apoB 和 AD 生物标志物淀粉样蛋白 β（Aβ）、总 tau（t-tau）和磷酸化 tau（p-tau）、突触标志物 GAP43、突触结合蛋白 1（SYNAPTOTAGMIN-1）、突触体相关蛋白 25（SNAP-25）和神经颗粒素的蛋白水平。将 CSF apoB 水平与正电子发射断层扫描（PET）扫描测量的 Aβ（18F-NAV4694）和 Tau（flortaucipir）以及 6 至 8 年内的认知评估变化进行对比。
AD 参与者的 CSF apoB 水平升高，并与无症状个体中的 t-tau、p-tau 和四个突触标志物相关。在后一组中，CSF apoB 水平与内侧颞叶（entorhinal）、海马旁回（parahippocampal）和梭状回（fusiform）区域的 PET flortaucipir 结合相关。基线 CSF apoB 水平与纵向视觉空间认知下降相关。
CSF apoB 与无症状受试者中早期 tau 失调明显相关，并确定了有风险的个体，这些个体随着时间的推移容易出现视觉空间认知能力下降。
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