The impact of apolipoprotein E, type ∊4 allele on Alzheimer's disease pathological biomarkers: a comprehensive post-mortem pilot-analysis.

The apolipoprotein E type ∊4 allele (ApoE4) is known as the strongest genetic risk factor for Alzheimer's Disease (AD). Meanwhile, many aspects of its impact on AD pathology remain underexplored. This study conducts a systematic data analysisof donor data from the Seattle Alzheimer's Disea...

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Main Authors: Ziyu Wan, Tao Ma
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0303486
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author Ziyu Wan
Tao Ma
author_facet Ziyu Wan
Tao Ma
author_sort Ziyu Wan
collection DOAJ
description The apolipoprotein E type ∊4 allele (ApoE4) is known as the strongest genetic risk factor for Alzheimer's Disease (AD). Meanwhile, many aspects of its impact on AD pathology remain underexplored. This study conducts a systematic data analysisof donor data from the Seattle Alzheimer's Disease Brain Cell Atlas. Our investigation delves into the intricate interplay between identified biomarkers and their correlation with ApoE4 across all severities of AD. Employing Pearson R correlation, and one-way and two-way ANOVA tests, we elucidate the pathological changes in biomarkers and the altering effects of ApoE4. Remarkably, the phosphorylation of tau observed in neurofibrillary tangles (NFTs) marked by the AT8 antibody, emerges as the most correlated factor with other pathological biomarkers. This correlation is mediated by both tau and amyloid pathology, suggesting a higher hierarchical role in determining AD pathological effects than other biomarkers. However, non-ApoE4 carriers exhibit a more significant correlation with disease progression severity compared to ApoE4 carriers, though ApoE4 carriers demonstrate significance in exacerbating the effect of accumulating phosphorylated tau and amyloid plaques assessed by AT8 and 6E10 antibodies. Furthermore, our analysis does not observe dramatic neuronal changes in grey matter across the span of AD pathology. Glia activation, measured by Iba1 and GFAP, demonstrates an amyloid-specific correlation. This research marks the first human post-mortem analysis providing a comprehensive examination of prevailing AD biomarkers and their interconnectedness with pathology and ApoE4 genetic factor. Limitations in the study are acknowledged, underscoring the need for further exploration and refinement in future research endeavors.
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spelling doaj-art-c9f1d53715914a778d210020b5dff8da2025-02-12T05:31:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01202e030348610.1371/journal.pone.0303486The impact of apolipoprotein E, type ∊4 allele on Alzheimer's disease pathological biomarkers: a comprehensive post-mortem pilot-analysis.Ziyu WanTao MaThe apolipoprotein E type ∊4 allele (ApoE4) is known as the strongest genetic risk factor for Alzheimer's Disease (AD). Meanwhile, many aspects of its impact on AD pathology remain underexplored. This study conducts a systematic data analysisof donor data from the Seattle Alzheimer's Disease Brain Cell Atlas. Our investigation delves into the intricate interplay between identified biomarkers and their correlation with ApoE4 across all severities of AD. Employing Pearson R correlation, and one-way and two-way ANOVA tests, we elucidate the pathological changes in biomarkers and the altering effects of ApoE4. Remarkably, the phosphorylation of tau observed in neurofibrillary tangles (NFTs) marked by the AT8 antibody, emerges as the most correlated factor with other pathological biomarkers. This correlation is mediated by both tau and amyloid pathology, suggesting a higher hierarchical role in determining AD pathological effects than other biomarkers. However, non-ApoE4 carriers exhibit a more significant correlation with disease progression severity compared to ApoE4 carriers, though ApoE4 carriers demonstrate significance in exacerbating the effect of accumulating phosphorylated tau and amyloid plaques assessed by AT8 and 6E10 antibodies. Furthermore, our analysis does not observe dramatic neuronal changes in grey matter across the span of AD pathology. Glia activation, measured by Iba1 and GFAP, demonstrates an amyloid-specific correlation. This research marks the first human post-mortem analysis providing a comprehensive examination of prevailing AD biomarkers and their interconnectedness with pathology and ApoE4 genetic factor. Limitations in the study are acknowledged, underscoring the need for further exploration and refinement in future research endeavors.https://doi.org/10.1371/journal.pone.0303486
spellingShingle Ziyu Wan
Tao Ma
The impact of apolipoprotein E, type ∊4 allele on Alzheimer's disease pathological biomarkers: a comprehensive post-mortem pilot-analysis.
PLoS ONE
title The impact of apolipoprotein E, type ∊4 allele on Alzheimer's disease pathological biomarkers: a comprehensive post-mortem pilot-analysis.
title_full The impact of apolipoprotein E, type ∊4 allele on Alzheimer's disease pathological biomarkers: a comprehensive post-mortem pilot-analysis.
title_fullStr The impact of apolipoprotein E, type ∊4 allele on Alzheimer's disease pathological biomarkers: a comprehensive post-mortem pilot-analysis.
title_full_unstemmed The impact of apolipoprotein E, type ∊4 allele on Alzheimer's disease pathological biomarkers: a comprehensive post-mortem pilot-analysis.
title_short The impact of apolipoprotein E, type ∊4 allele on Alzheimer's disease pathological biomarkers: a comprehensive post-mortem pilot-analysis.
title_sort impact of apolipoprotein e type ∊4 allele on alzheimer s disease pathological biomarkers a comprehensive post mortem pilot analysis
url https://doi.org/10.1371/journal.pone.0303486
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