Plasma Biomarkers of Alzheimer Disease in Women With and Without HIV.
Plasma Biomarkers of Alzheimer Disease in Women With and Without HIV.
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DOI：
10.1001/jamanetworkopen.2023.44194
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发表时间：
2023-11-01
影响因子：
13.8
通讯作者：
Gustafson, Deborah R.
中科院分区：
文献类型：
--
作者：
Li, Xuantao;Yucel, Recai;Clervius, Helene;Kamalakar, Kundun;Zetterberg, Henrik;Blennow, Kaj;Zhang, Jinbing;Adimora, Adaora;Collins, Lauren F.;Fischl, Margaret;Kassaye, Seble;Maki, Pauline;Seaberg, Eric;Sharma, Anjali;Vance, David;Gustafson, Deborah R.
这项队列研究分析了阿尔茨海默病的生物标志物是否与感染和未感染艾滋病毒的女性的神经心理表现相关。
基于血液的阿尔茨海默病（AD）生物标志物是否与在研究中社会人口统计学上代表性不足的感染和未感染艾滋病毒的女性的神经心理表现相关？
这项对294名感染艾滋病毒的女性和98名未感染艾滋病毒的女性进行的队列研究发现，淀粉样蛋白-β（Aβ）、tau蛋白和神经退行性变（Aβ40、Aβ42、总tau蛋白、磷酸化tau 231和神经丝轻链）生物标志物的横断面和1年变化与特定领域的神经心理表现相关。
这些研究结果表明，测量与神经心理表现相关的基于血液的生物标志物可能是监测感染和未感染艾滋病毒的女性大脑衰老健康和阿尔茨海默病发展的关键进展。
与阿尔茨海默病（AD）风险增加相关的基于血液的生物标志物在感染和未感染艾滋病毒的人群中，特别是女性中研究不足。
为了确定血浆淀粉样蛋白-β40（Aβ40）、Aβ42、Aβ42与Aβ40的比值、总tau蛋白（t - tau）、磷酸化tau 231（p - tau231）、胶质纤维酸性蛋白（GFAP）和/或神经丝轻链（NFL）的基线或1年变化是否与感染艾滋病毒的女性（WLWH）和未感染艾滋病毒的女性（WLWOH）的神经心理表现（NP）相关。
这项纵向、前瞻性队列研究在2017年至2019年期间进行了1年的重复临床测量（NP仅测量一次）和生物样本采集。参与者是来自美国各地城市10个临床研究站点的40岁及以上女性，她们是妇女机构间艾滋病毒研究的一部分。数据分析于2022年4月至12月进行。
实验室确诊的艾滋病毒感染状况和阿尔茨海默病生物标志物。
经过社会人口统计学调整的NP T分数（注意力和工作记忆、执行功能、处理速度、记忆、学习、语言流畅性、运动功能和整体表现）是主要观察结果。测量并分析了基线和1年空腹血浆Aβ40、Aβ42、t - tau、p - tau231、GFAP和NFL水平，采用多变量线性回归分析。
该研究包括307名参与者（294名年龄≥50岁[96%]；164名非裔美国人或黑人女性[53%]；214名具有高中或更高学历的女性[70%]；238名当前或曾经吸烟的女性[78%]；236名超重或肥胖的女性[体重指数>25][77%]），其中包括209名WLWH和98名WLWOH。与基线时的WLWOH相比，WLWH在学习（平均[标准差]T分数47.8[11.3]对51.4[10.5]）、记忆（平均[标准差]T分数48.3[11.6]对52.4[10.2]）、语言流畅性（平均[标准差]T分数48.3[9.8]对50.7[8.5]）和整体（平均[标准差]T分数49.2[6.8]对51.1[5.9]）NP评估中表现更差。WLWH的基线中位Aβ40、GFAP和NFL水平高于WLWOH。艾滋病毒血清学状态在1年生物标志物变化方面没有差异。在整个样本中，较低的学习、记忆和运动NP与1年Aβ40增加相关；较低的学习和运动与Aβ42增加相关；较低的运动与p - tau231增加相关；较低的处理速度、语言流畅性和运动与NFL增加相关。在WLWH中，从基线到随访1年Aβ40增加与较差的学习、记忆和整体NP相关；1年t - tau增加与较差的执行功能相关；1年NFL增加与较差的处理速度相关。在WLWOH中，1年Aβ40和Aβ42增加与较差的记忆表现相关，NFL增加与较差的运动表现相关。
这些研究结果表明，某些血浆阿尔茨海默病生物标志物的增加与WLWH和WLWOH的NP相关，可能与阿尔茨海默病的后期发病相关，测量这些生物标志物可能是监测感染和未感染艾滋病毒的女性大脑衰老健康和阿尔茨海默病发展的关键进展。
This cohort study analyzes whether biomarkers for Alzheimer disease are associated with neuropsychological performance among women with and without HIV. Are blood-based biomarkers for Alzheimer disease (AD) associated with neuropsychological performance in women with and without HIV who are also sociodemographically underrepresented in research? This cohort study of 294 women with HIV and 98 women without HIV found that cross-sectional and 1-year changes in biomarkers of amyloid-β (Aβ), tau, and neurodegeneration (Aβ40, Aβ42, total-tau, phosphorylated tau 231, and neurofilament light chain) were associated with domain-specific neuropsychological performance. These findings suggest that measuring blood-based biomarkers associated with neuropsychological performance could be a pivotal advancement in monitoring aging brain health and development of AD among women with and without HIV. Blood-based biomarkers associated with increased risk of Alzheimer disease (AD) are understudied in people living with and without HIV, particularly women. To determine whether baseline or 1-year changes in plasma amyloid-β40 (Aβ40), Aβ42, ratio of Aβ42 to Aβ40, total tau (t-tau), phosphorylated tau 231 (p-tau231), glial fibrillary acidic protein (GFAP), and/or neurofilament light chain (NFL) are associated with neuropsychological performance (NP) among women living with HIV (WLWH) and women living without HIV (WLWOH). This longitudinal, prospective, cohort study with 1-year repeated clinical measures (NP only measured once) and biospecimen collection occurred between 2017 and 2019. Participants were women aged 40 years or older from 10 clinical research sites in cities across the US that were part of the Women’s Interagency HIV Study. Data analysis was conducted from April to December 2022. Laboratory-confirmed HIV status and AD biomarkers. Sociodemographically adjusted NP T-scores (attention and working memory, executive function, processing speed, memory, learning, verbal fluency, motor function, and global performance) were the primary outcomes. Baseline and 1-year fasting plasma Aβ40, Aβ42, t-tau, p-tau231, GFAP, and NFL levels were measured and analyzed using multivariable linear regression. The study consisted of 307 participants (294 aged ≥50 years [96%]; 164 African American or Black women [53%]; 214 women with a high school education or higher [70%]; 238 women who were current or former smokers [78%]; and 236 women [77%] who were overweight or obese [body mass index >25]) including 209 WLWH and 98 WLWOH. Compared with WLWOH at baseline, WLWH performed worse on learning (mean [SD] T-score 47.8 [11.3] vs 51.4 [10.5]), memory (mean [SD] T-score 48.3 [11.6] vs 52.4 [10.2]), verbal fluency (mean [SD] T-score 48.3 [9.8] vs 50.7 [8.5]), and global (mean [SD] T-score 49.2 [6.8] vs 51.1 [5.9]) NP assessments. Baseline median Aβ40, GFAP, and NFL levels were higher among WLWH vs WLWOH. There were no differences in 1-year biomarker change by HIV serostatus. Lower learning, memory, and motor NP were associated with 1-year Aβ40 increase; lower learning and motor with Aβ42 increase; lower motor with p-tau231 increase; and lower processing speed, verbal fluency and motor with NFL increase in the entire sample. Among WLWH, a 1-year increase in Aβ40 from baseline to follow-up was associated with worse learning, memory, and global NP; a 1-year increase in t-tau with worse executive function; and a 1-year increase in NFL with worse processing speed. Among WLWOH, a 1-year increase in Aβ40 and Aβ42 were associated with poorer memory performance and NFL was associated with poorer motor performance. These findings suggest that increases in certain plasma AD biomarkers are associated with NP in WLWH and WLWOH and may be associated with later onset of AD, and measuring these biomarkers could be a pivotal advancement in monitoring aging brain health and development of AD among women with and without HIV.
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影响因子：
3.2
作者：
Anderson AM;Easley KA;Kasher N;Franklin D;Heaton RK;Zetterberg H;Blennow K;Gisslen M;Letendre SL
通讯作者：
Letendre SL
影响因子：
12.7
作者：
Ashton NJ;Pascoal TA;Karikari TK;Benedet AL;Lantero-Rodriguez J;Brinkmalm G;Snellman A;Schöll M;Troakes C;Hye A;Gauthier S;Vanmechelen E;Zetterberg H;Rosa-Neto P;Blennow K
通讯作者：
Blennow K
DOI：
10.15585/mmwr.mm6946a1
发表时间：
2020-11-20
期刊：
MMWR. Morbidity and mortality weekly report
影响因子：
--
作者：
Bosh KA;Johnson AS;Hernandez AL;Prejean J;Taylor J;Wingard R;Valleroy LA;Hall HI
通讯作者：
Hall HI
影响因子：
11
作者：
Gustafson, Deborah R.;Skoog, Ingmar;Blennow, Kaj
通讯作者：
Blennow, Kaj
DOI：
10.1097/qai.0000000000002484
发表时间：
2020-12-15
期刊：
Journal of acquired immune deficiency syndromes (1999)
影响因子：
--
作者：
Anderson AM;Jang JH;Easley KA;Fuchs D;Gisslen M;Zetterberg H;Blennow K;Ellis RJ;Franklin D;Heaton RK;Grant I;Letendre SL
通讯作者：
Letendre SL