血浆神经丝轻链与脑内病理及认知在非痴呆的常染色体显性阿尔茨海默病个体中的相关性。
Associations between plasma neurofilament light, in vivo brain pathology, and cognition in non-demented individuals with autosomal-dominant Alzheimer's disease.
机构信息
Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
出版信息
Alzheimers Dement. 2021 May;17(5):813-821. doi: 10.1002/alz.12248. Epub 2021 Feb 1.
Abstract
BACKGROUND
Neurofilament light (NfL) is a promising biomarker of early neurodegeneration in Alzheimer's disease (AD). We examined whether plasma NfL was associated with in vivo amyloid beta and tau, and cognitive performance in non-demented presenilin-1 (PSEN1) E280A mutation carriers.
METHODS
Twenty-five mutation carriers and 19 non-carriers (age range: 28 to 49 years) were included in this study. Participants underwent 11C Pittsburgh compound B (PiB)-PET (positron emission tomography), flortaucipir-PET, blood sampling, and cognitive testing.
RESULTS
Mutation carriers exhibited higher plasma NfL levels than non-carriers. In carriers, higher NfL levels were related to greater regional tau burden and worse cognition, but not amyloid beta load. When we adjusted for age, a proxy of disease progression, elevated plasma NfL levels were only correlated with worse memory recall.
CONCLUSIONS
Findings support an association between plasma NfL, cognition, and tau pathology in non-demented individuals at genetic risk for developing AD dementia. Plasma NfL may be useful for selecting individuals at increased risk and tracking disease progression in AD.
摘要
背景
神经丝轻链（NfL）是阿尔茨海默病（AD）早期神经退行性变的有前途的生物标志物。我们研究了血浆 NfL 是否与体内淀粉样β和 tau 以及无痴呆早老素-1（PSEN1）E280A 突变携带者的认知表现有关。
方法
本研究纳入了 25 名突变携带者和 19 名非携带者（年龄范围：28 至 49 岁）。参与者接受了 11C 匹兹堡复合物 B（PiB）-正电子发射断层扫描（PET）、flortaucipir-PET、采血和认知测试。
结果
突变携带者的血浆 NfL 水平高于非携带者。在携带者中，较高的 NfL 水平与更大的区域 tau 负担和更差的认知有关，但与淀粉样β负荷无关。当我们调整年龄（疾病进展的替代指标）时，升高的血浆 NfL 水平仅与较差的记忆回忆有关。
结论
这些发现支持在有患 AD 痴呆遗传风险的非痴呆个体中，血浆 NfL、认知和 tau 病理学之间存在关联。血浆 NfL 可能有助于选择风险增加的个体并跟踪 AD 中的疾病进展。
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