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Plasma Biomarkers of Alzheimer Disease in Women With and Without HIV

IMPORTANCE: Blood-based biomarkers associated with increased risk of Alzheimer disease (AD) are understudied in people living with and without HIV, particularly women. OBJECTIVE: To determine whether baseline or 1-year changes in plasma amyloid-β40 (Aβ40), Aβ42, ratio of Aβ42 to Aβ40, total tau (t-t...

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Autores principales: Li, Xuantao, Yucel, Recai, Clervius, Helene, Kamalakar, Kundun, Zetterberg, Henrik, Blennow, Kaj, Zhang, Jinbing, Adimora, Adaora, Collins, Lauren, Fischl, Margaret, Kassaye, Seble, Maki, Pauline, Seaberg, Eric, Sharma, Anjali, Vance, David, Gustafson, Deborah R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687654/
https://www.ncbi.nlm.nih.gov/pubmed/38019518
http://dx.doi.org/10.1001/jamanetworkopen.2023.44194
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author Li, Xuantao
Yucel, Recai
Clervius, Helene
Kamalakar, Kundun
Zetterberg, Henrik
Blennow, Kaj
Zhang, Jinbing
Adimora, Adaora
Collins, Lauren
Fischl, Margaret
Kassaye, Seble
Maki, Pauline
Seaberg, Eric
Sharma, Anjali
Vance, David
Gustafson, Deborah R.
author_facet Li, Xuantao
Yucel, Recai
Clervius, Helene
Kamalakar, Kundun
Zetterberg, Henrik
Blennow, Kaj
Zhang, Jinbing
Adimora, Adaora
Collins, Lauren
Fischl, Margaret
Kassaye, Seble
Maki, Pauline
Seaberg, Eric
Sharma, Anjali
Vance, David
Gustafson, Deborah R.
author_sort Li, Xuantao
collection PubMed
description IMPORTANCE: Blood-based biomarkers associated with increased risk of Alzheimer disease (AD) are understudied in people living with and without HIV, particularly women. OBJECTIVE: 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-tau(231)), 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). DESIGN, SETTING, AND PARTICIPANTS: 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. EXPOSURE: Laboratory-confirmed HIV status and AD biomarkers. MAIN OUTCOMES AND MEASURES: 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-tau(231), GFAP, and NFL levels were measured and analyzed using multivariable linear regression. RESULTS: 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-tau(231) 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. CONCLUSIONS AND RELEVANCE: 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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spelling pubmed-106876542023-12-01 Plasma Biomarkers of Alzheimer Disease in Women With and Without HIV Li, Xuantao Yucel, Recai Clervius, Helene Kamalakar, Kundun Zetterberg, Henrik Blennow, Kaj Zhang, Jinbing Adimora, Adaora Collins, Lauren Fischl, Margaret Kassaye, Seble Maki, Pauline Seaberg, Eric Sharma, Anjali Vance, David Gustafson, Deborah R. JAMA Netw Open Original Investigation IMPORTANCE: Blood-based biomarkers associated with increased risk of Alzheimer disease (AD) are understudied in people living with and without HIV, particularly women. OBJECTIVE: 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-tau(231)), 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). DESIGN, SETTING, AND PARTICIPANTS: 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. EXPOSURE: Laboratory-confirmed HIV status and AD biomarkers. MAIN OUTCOMES AND MEASURES: 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-tau(231), GFAP, and NFL levels were measured and analyzed using multivariable linear regression. RESULTS: 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-tau(231) 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. CONCLUSIONS AND RELEVANCE: 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. American Medical Association 2023-11-29 /pmc/articles/PMC10687654/ /pubmed/38019518 http://dx.doi.org/10.1001/jamanetworkopen.2023.44194 Text en Copyright 2023 Li X et al. JAMA Network Open. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the CC-BY License.
spellingShingle Original Investigation
Li, Xuantao
Yucel, Recai
Clervius, Helene
Kamalakar, Kundun
Zetterberg, Henrik
Blennow, Kaj
Zhang, Jinbing
Adimora, Adaora
Collins, Lauren
Fischl, Margaret
Kassaye, Seble
Maki, Pauline
Seaberg, Eric
Sharma, Anjali
Vance, David
Gustafson, Deborah R.
Plasma Biomarkers of Alzheimer Disease in Women With and Without HIV
title Plasma Biomarkers of Alzheimer Disease in Women With and Without HIV
title_full Plasma Biomarkers of Alzheimer Disease in Women With and Without HIV
title_fullStr Plasma Biomarkers of Alzheimer Disease in Women With and Without HIV
title_full_unstemmed Plasma Biomarkers of Alzheimer Disease in Women With and Without HIV
title_short Plasma Biomarkers of Alzheimer Disease in Women With and Without HIV
title_sort plasma biomarkers of alzheimer disease in women with and without hiv
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687654/
https://www.ncbi.nlm.nih.gov/pubmed/38019518
http://dx.doi.org/10.1001/jamanetworkopen.2023.44194
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