Clinical and neuropathological associations of plasma Aβ₄₂/Aβ₄₀, p-tau217 and neurofilament light in sporadic frontotemporal dementia spectrum disorders.

IF 4 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2025-01-29 eCollection Date: 2025-01-01 DOI:10.1002/dad2.70078

Binita Rajbanshi, Igor Prufer Q C Araujo, Lawren VandeVrede, Peter A Ljubenkov, Adam M Staffaroni, Hilary W Heuer, Argentina Lario Lago, Eliana Marisa Ramos, Leonard Petrucelli, Tania Gendron, Jeffrey L Dage, William W Seeley, Lea T Grinberg, Salvatore Spina, Randall J Bateman, Howard J Rosen, Bradley F Boeve, Adam L Boxer, Julio C Rojas

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引用次数: 0

Abstract

Introduction: Plasma amyloid beta₄₂/amyloid beta₄₀ (Aβ₄₂/Aβ₄₀) and phosphorylated tau217 (p-tau217) identify individuals with primary Alzheimer's disease (AD). They may detect AD co-pathology in the setting of other primary neurodegenerative diseases, but this has not been systematically studied.

Methods: We compared the clinical, neuroimaging, and neuropathological associations of plasma Aβ₄₂/Aβ₄₀ (mass spectrometry), p-tau217 (electrochemiluminescence), and neurofilament light ([NfL], single molecule array [Simoa]), as markers of AD co-pathology, in a sporadic frontotemporal dementia (FTD) cohort (n = 620).

Results: Aβ₄₂/Aβ₄₀ showed no clinicopathological associations. High p-tau217 was present in amnestic dementia (AmD) presumed to be due to FTD, logopenic primary progressive aphasia (lvPPA), and APOEε4 carriers, and correlated with worse baseline and longitudinal clinical scores, lower hippocampal volumes, and more severe AD co-pathology (Braak Stage). NfL was elevated in all FTD phenotypes, and correlated with clinical scores and frontotemporal brain volumes.

Discussion: Plasma p-tau217 has clinical, neuroimaging, and neuropathological correlates in sporadic FTD and may identify FTD cases with AD co-pathology.

Highlights: Alzheimer's disease (AD) features could be identified with plasma phosphorylated tau217 (p-tau217) in frontotemporal lobar degeneration (FTLD).Plasma p-tau217 is a better discriminator of AD co-pathology and AD-associated features in FTLD than plasma amyloid beta₄₂/amyloid beta₄₀ (Aβ₄₂/Aβ₄₀) and neurofilament light (NfL).In FTLD, plasma p-tau217, but not Aβ₄₂/Aβ₄₀ or neurofilament light, has phenotypical, neurocognitive, and neuroimaging correlates suggestive of AD co-pathology.

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散发性额颞叶痴呆谱系障碍患者血浆a - β42/ a - β40、p-tau217和神经丝光的临床和神经病理关系

血浆淀粉样蛋白β42/ β40 （Aβ42/Aβ40）和磷酸化的tau217 （p-tau217）可识别原发性阿尔茨海默病（AD）个体。他们可能在其他原发性神经退行性疾病的背景下发现AD的共同病理，但这还没有系统的研究。方法：我们比较了散发性额颞叶痴呆（FTD）队列（n = 620）中血浆a - β42/ a - β40（质谱）、p-tau217（电化学发光）和神经丝光（[NfL]、单分子阵列[Simoa]）作为AD共同病理标志物的临床、神经影像学和神经病理学相关性。结果：Aβ42/Aβ40无临床病理相关性。高p-tau217存在于被认为是由FTD、记忆缺乏性原发性进行性失语症（lvPPA）和APOEε4携带者引起的遗忘性痴呆（AmD）中，并与较差的基线和纵向临床评分、较低的海马体积和更严重的AD共病理（Braak期）相关。NfL在所有FTD表型中均升高，并与临床评分和额颞叶脑容量相关。讨论：血浆p-tau217在散发性FTD中具有临床、神经影像学和神经病理学相关性，可以识别伴有AD共病理的FTD病例。重点：阿尔茨海默病（AD）的特征可以通过额颞叶变性（FTLD）中血浆磷酸化的tau217 （p-tau217）来识别。血浆p-tau217比血浆β42/ β40 （a - β42/ a - β40）和神经丝光（NfL）更好地鉴别FTLD中AD共病理和AD相关特征。在FTLD中，血浆p-tau217，而不是a - β42/ a - β40或神经丝光，具有提示AD共病理的表型、神经认知和神经影像学相关。

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来源期刊

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Medicine-Psychiatry and Mental Health

CiteScore

7.80

自引率

7.50%

发文量

101

审稿时长

8 weeks

期刊介绍： Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) is an open access, peer-reviewed, journal from the Alzheimer''s Association® that will publish new research that reports the discovery, development and validation of instruments, technologies, algorithms, and innovative processes. Papers will cover a range of topics interested in the early and accurate detection of individuals with memory complaints and/or among asymptomatic individuals at elevated risk for various forms of memory disorders. The expectation for published papers will be to translate fundamental knowledge about the neurobiology of the disease into practical reports that describe both the conceptual and methodological aspects of the submitted scientific inquiry. Published topics will explore the development of biomarkers, surrogate markers, and conceptual/methodological challenges. Publication priority will be given to papers that 1) describe putative surrogate markers that accurately track disease progression, 2) biomarkers that fulfill international regulatory requirements, 3) reports from large, well-characterized population-based cohorts that comprise the heterogeneity and diversity of asymptomatic individuals and 4) algorithmic development that considers multi-marker arrays (e.g., integrated-omics, genetics, biofluids, imaging, etc.) and advanced computational analytics and technologies.