Plasma p-tau181 shows stronger network association to Alzheimer's disease dementia than neurofilament light and total tau

被引：26

作者：

Frank, Brandon ^{[1
,2
,3
]}

Ally, Madeline ^{[1
,2
]}

Brekke, Bailee ^{[1
,2
]}

Zetterberg, Henrik ^{[4
,5
,6
,7
]}

Blennow, Kaj ^{[6
,7
]}

Sugarman, Michael A. ^{[1
,2
,3
]}

Ashton, Nicholas J. ^{[6
,7
]}

Karikari, Thomas K. ^{[6
,7
]}

Tripodis, Yorghos ^{[1
,2
,8
]}

Martin, Brett ^{[1
,2
,12
]}

Palmisano, Joseph N. ^{[1
,2
,12
]}

Steinberg, Eric G. ^{[1
,2
]}

Simkina, Irene ^{[13
]}

Turk, Katherine W. ^{[1
,2
,9
,11
]}

Budson, Andrew E. ^{[1
,2
,9
,11
]}

O'Connor, Maureen K. ^{[1
,2
,3
]}

Au, Rhoda ^{[1
,2
,9
,14
,16
,17
]}

Goldstein, Lee E. ^{[1
,2
,10
,18
,19
,20
,21
,22
]}

Jun, Gyungah R. ^{[13
]}

Kowall, Neil W. ^{[1
,2
,9
,10
,11
]}

Stein, Thor D. ^{[1
,2
,3
,10
,11
]}

McKee, Ann C. ^{[1
,2
,3
,9
,10
,11
]}

Killiany, Ronald ^{[1
,2
,9
,14
,15
]}

Qiu, Wei Qiao ^{[1
,2
,18
,23
]}

Stern, Robert A. ^{[1
,2
,9
,14
,24
]}

Mez, Jesse ^{[1
,2
,9
,16
]}

Alosco, Michael L. ^{[1
,2
,9
]}

机构：

[1] Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02118 USA

[2] Boston Univ, CTE Ctr, Sch Med, Boston, MA 02118 USA

[3] US Dept Vet Affairs, VA Bedford Healthcare Syst, Bedford, MA USA

[4] UCL Inst Neurol, Dept Neurodegenerat Dis, London, England

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

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

[7] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Gothenburg, Sweden

[8] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[9] Boston Univ, Sch Med, Dept Neurol, Boston, MA USA

[10] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA

[11] US Dept Vet Affairs, VA Boston Healthcare Syst, Jamaica Plain, MA USA

[12] Boston Univ, Sch Publ Hlth, Biostat & Epidemiol Data Analyt Ctr, Boston, MA USA

[13] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA

[14] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA

[15] Boston Univ, Sch Med, Ctr Biomed Imaging, Boston, MA 02118 USA

[16] Boston Univ, Sch Med, Framingham Heart Study, Boston, MA 02118 USA

[17] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[18] Boston Univ, Sch Med, Dept Psychiat, Boston, MA USA

[19] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA

[20] Boston Univ, Coll Engn, Dept Biomed Engn, Boston, MA 02215 USA

[21] Boston Univ, Coll Engn, Dept Elect Engn, Boston, MA 02215 USA

[22] Boston Univ, Coll Engn, Dept Comp Engn, Boston, MA 02215 USA

[23] Boston Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02118 USA

[24] Boston Univ, Sch Med, Dept Neurosurg, Boston, MA 02118 USA

来源：

ALZHEIMERS & DEMENTIA | 2022年 / 18卷 / 08期

基金：

瑞典研究理事会; 欧洲研究理事会; 英国医学研究理事会; 欧盟地平线“2020”; 美国国家卫生研究院;

关键词：

Alzheimer's Disease; P-tau; Plasma biomarkers; Network analysis; Neuropsychology; MILD COGNITIVE IMPAIRMENT; CSF-PHOSPHORYLATED-TAU; NATIONAL INSTITUTE; DIAGNOSTIC GUIDELINES; RESEARCH FRAMEWORK; PROTEIN; BIOMARKERS; RECOMMENDATIONS; THREONINE-231; PATHOLOGIES;

D O I：

10.1002/alz.12508

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Introduction We examined the ability of plasma hyperphosphorylated tau (p-tau)(181) to detect cognitive impairment due to Alzheimer's disease (AD) independently and in combination with plasma total tau (t-tau) and neurofilament light (NfL). Methods Plasma samples were analyzed using the Simoa platform for 235 participants with normal cognition (NC), 181 with mild cognitive impairment due to AD (MCI), and 153 with AD dementia. Statistical approaches included multinomial regression and Gaussian graphical models (GGMs) to assess a network of plasma biomarkers, neuropsychological tests, and demographic variables. Results Plasma p-tau(181) discriminated AD dementia from NC, but not MCI, and correlated with dementia severity and worse neuropsychological test performance. Plasma NfL similarly discriminated diagnostic groups. Unlike plasma NfL or t-tau, p-tau(181) had a direct association with cognitive diagnosis in a bootstrapped GGM. Discussion These results support plasma p-tau(181) for the detection of AD dementia and the use of blood-based biomarkers for optimal disease detection.

引用

页码：1523 / 1536

页数：14

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