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CSF Apo-E levels associate with cognitive decline and MRI changes.

Abstract

Apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for Alzheimer's disease (AD) and it is thought to do so by modulating levels of its product, apolipoprotein E (Apo-E), and regulating amyloid-β (Aβ) clearance. However, information on clinical and biomarker correlates of Apo-E proteins is scarce. We examined the relationship of cerebrospinal fluid (CSF) and plasma Apo-E protein levels, and APOE genotype to cognition and AD biomarker changes in 311 AD neuroimaging initiative subjects with CSF Apo-E measurements and 565 subjects with plasma Apo-E measurements. At baseline, higher CSF Apo-E levels were associated with higher total and phosphorylated CSF tau levels. CSF Apo-E levels were associated with longitudinal cognitive decline, MCI conversion to dementia, and gray matter atrophy rate in total tau/Aβ1-42 ratio and APOE genotype-adjusted analyses. In analyses stratified by APOE genotype, our results were only significant in the group without the ε4 allele. Baseline CSF Apo-E levels did not predict longitudinal CSF Aβ or tau changes. Plasma Apo-E levels show a mild correlation with CSF Apo-E levels, but were not associated with longitudinal cognitive and MRI changes. Based on our analyses, we speculate that increased CSF Apo-E2 or -E3 levels might represent a protective response to injury in AD and may have neuroprotective effects by decreasing neuronal damage independent of tau and amyloid deposition in addition to its effects on amyloid clearance.

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  • Authors+Show Affiliations

    ,

    Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, HUP, Maloney 3rd, 36th and Spruce Streets, Philadelphia, PA, 19104-4283, USA.

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    Source

    Acta neuropathologica 127:5 2014 May pg 621-32

    MeSH

    Aged
    Alzheimer Disease
    Amyloid beta-Peptides
    Apolipoproteins E
    Atrophy
    Biomarkers
    Brain
    Cognition
    Cognitive Dysfunction
    Disease Progression
    Female
    Follow-Up Studies
    Gray Matter
    Humans
    Longitudinal Studies
    Magnetic Resonance Imaging
    Male
    Peptide Fragments
    Phosphorylation
    Severity of Illness Index
    Survival Analysis
    tau Proteins

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    24385135

    Citation

    Toledo, Jon B., et al. "CSF Apo-E Levels Associate With Cognitive Decline and MRI Changes." Acta Neuropathologica, vol. 127, no. 5, 2014, pp. 621-32.
    Toledo JB, Da X, Weiner MW, et al. CSF Apo-E levels associate with cognitive decline and MRI changes. Acta Neuropathol. 2014;127(5):621-32.
    Toledo, J. B., Da, X., Weiner, M. W., Wolk, D. A., Xie, S. X., Arnold, S. E., ... Trojanowski, J. Q. (2014). CSF Apo-E levels associate with cognitive decline and MRI changes. Acta Neuropathologica, 127(5), pp. 621-32. doi:10.1007/s00401-013-1236-0.
    Toledo JB, et al. CSF Apo-E Levels Associate With Cognitive Decline and MRI Changes. Acta Neuropathol. 2014;127(5):621-32. PubMed PMID: 24385135.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - CSF Apo-E levels associate with cognitive decline and MRI changes. AU - Toledo,Jon B, AU - Da,Xiao, AU - Weiner,Michael W, AU - Wolk,David A, AU - Xie,Sharon X, AU - Arnold,Steven E, AU - Davatzikos,Christos, AU - Shaw,Leslie M, AU - Trojanowski,John Q, AU - ,, Y1 - 2014/01/03/ PY - 2013/10/23/received PY - 2013/12/17/accepted PY - 2013/12/16/revised PY - 2014/1/4/entrez PY - 2014/1/5/pubmed PY - 2014/12/15/medline SP - 621 EP - 32 JF - Acta neuropathologica JO - Acta Neuropathol. VL - 127 IS - 5 N2 - Apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for Alzheimer's disease (AD) and it is thought to do so by modulating levels of its product, apolipoprotein E (Apo-E), and regulating amyloid-β (Aβ) clearance. However, information on clinical and biomarker correlates of Apo-E proteins is scarce. We examined the relationship of cerebrospinal fluid (CSF) and plasma Apo-E protein levels, and APOE genotype to cognition and AD biomarker changes in 311 AD neuroimaging initiative subjects with CSF Apo-E measurements and 565 subjects with plasma Apo-E measurements. At baseline, higher CSF Apo-E levels were associated with higher total and phosphorylated CSF tau levels. CSF Apo-E levels were associated with longitudinal cognitive decline, MCI conversion to dementia, and gray matter atrophy rate in total tau/Aβ1-42 ratio and APOE genotype-adjusted analyses. In analyses stratified by APOE genotype, our results were only significant in the group without the ε4 allele. Baseline CSF Apo-E levels did not predict longitudinal CSF Aβ or tau changes. Plasma Apo-E levels show a mild correlation with CSF Apo-E levels, but were not associated with longitudinal cognitive and MRI changes. Based on our analyses, we speculate that increased CSF Apo-E2 or -E3 levels might represent a protective response to injury in AD and may have neuroprotective effects by decreasing neuronal damage independent of tau and amyloid deposition in addition to its effects on amyloid clearance. SN - 1432-0533 UR - https://www.unboundmedicine.com/medline/citation/24385135/CSF_Apo_E_levels_associate_with_cognitive_decline_and_MRI_changes_ L2 - https://dx.doi.org/10.1007/s00401-013-1236-0 DB - PRIME DP - Unbound Medicine ER -