Association of Plasma Neurofilament Light Chain with Neocortical Amyloid-β Load and Cognitive Performance in Cognitively Normal Elderly Participants

被引：57

作者：

Chatterjee, Pratishtha ^{[1
,2
,3
]}

Goozee, Kathryn ^{[1
,2
,3
,4
,5
,7
]}

Sohrabi, Hamid R. ^{[1
,2
,3
,5
,6
]}

Shen, Kaikai ^{[8
]}

Shah, Tejal ^{[1
,2
,6
]}

Asih, Prita R. ^{[3
,9
]}

Dave, Preeti ^{[1
,4
]}

ManYan, Candice ^{[4
]}

Taddei, Kevin ^{[2
,6
]}

Chung, Roger ^{[1
]}

Zetterberg, Henrik ^{[10
,11
,12
,13
]}

Blennow, Kaj ^{[10
,11
]}

Martins, Ralph N. ^{[1
,2
,3
,5
,6
,7
]}

机构：

[1] Macquarie Univ, Dept Biomed Sci, N Ryde, NSW, Australia

[2] Edith Cowan Univ, Sch Med Hlth & Sci, Joondalup, WA, Australia

[3] KaRa Inst Neurol Dis, Macquarie Pk, Sydney, NSW, Australia

[4] Anglicare, Dept Clin Res, Castle Hill, NSW, Australia

[5] Univ Western Australia, Sch Psychiat & Clin Neurosci, Crawley, WA, Australia

[6] Australian Alzheimer Res Fdn, Nedlands, WA, Australia

[7] Cooperat Res Ctr Mental Hlth, Carlton, Australia

[8] CSIRO, Australian eHlth Res, Floreat, Australia

[9] Univ New South Wales, Sch Med Sci, Kensington, NSW, Australia

[10] Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden

[11] Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden

[12] UCL Inst Neurol, Dept Mol Neurosci, Queen Sq, London, England

[13] UCL, UK Dementia Res Inst, London, England

来源：

JOURNAL OF ALZHEIMERS DISEASE | 2018年 / 63卷 / 02期

基金：

瑞典研究理事会;

关键词：

Alzheimer's disease; blood; neurofilaments; positron emission tomography; cognitive function; episodic memory; executive function; verbal memory; visual memory; PRECLINICAL ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; FRONTOTEMPORAL DEMENTIA; DIFFERENTIAL-DIAGNOSIS; NEURODEGENERATION; DEGENERATION; BIOMARKERS; DISORDER;

D O I：

10.3233/JAD-180025

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Background: The disruption of neurofilament, an axonal cytoskeletal protein, in neurodegenerative conditions may result in neuronal damage and its release into the cerebrospinal fluid and blood. In Alzheimer's disease (AD), neurofilament light chain (NFL), a neurofilament subunit, is elevated in the cerebrospinal fluid and blood. Objective: Investigate the association of plasma NFL with preclinical-AD features, such as high neocortical amyloid-beta load (NAL) and subjective memory complaints, and cognitive performance in cognitively normal older adults. Methods: Plasma NFL concentrations were measured employing the single molecule array platform in participants from the Kerr Anglican Retirement Village Initiative in Ageing Health cohort, aged 65-90 years. Participants underwent a battery of neuropsychological testing to evaluate cognitive performance and were categorized as low NAL (NAL-, n = 65) and high NAL (NAL+, n = 35) assessed via PET, and further stratified into subjective memory complainers (SMC; nNAL- = 51, nNAL+ = 25) and non-SMC (nNAL- = 14, nNAL+ = 10) based on the Memory Assessment Clinic-Questionnaire. Results: Plasma NFL inversely correlated with cognitive performance. No significant difference in NFL was observed between NAL+ and NAL-participants; however, within APOE epsilon 4 non-carriers, higher NAL was observed in individuals with NFL concentrations within quartiles 3 and 4 (versus quartile 1). Additionally, within the NAL+ participants, SMC had a trend of higher NFL compared to non-SMC. Conclusion: Plasma NFL is inversely associated with cognitive performance in elderly individuals. While plasma NFL may not reflect NAL in individuals with normal global cognition, the current observations indicate that onset of axonal injury, reflected by increased plasma NFL, within the preclinical phase of AD may contribute to the pathogenesis of AD.

引用

页码：479 / 487

页数：9

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