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Association of APOE with tau-tangle pathology with and without β-amyloid.

Abstract

This study tested the hypothesis that the association of apolipoprotein E (APOE) with paired helical filament tau (PHF-tau) tangle pathology differs in brains with and without β-amyloid. Participants were 1056 autopsied individuals from 2 clinical-pathologic cohort studies of aging and Alzheimer's disease (AD), the Religious Orders Study, and the Rush Memory and Aging Project. Neuropathologic measures were obtained using immunohistochemistry targeting β-amyloid and PHF-tau tangles in 8 brain regions. Linear regression was used to compare the relation of APOE ε4 and ε2 to PHF-tau-tangle density in persons with β-amyloid relative to persons without β-amyloid. We found an interaction between APOE ε4 carriers and presence of β-amyloid (β = -0.968, p = 0.013) such that the association of APOE ε4 with PHF-tau tangles was much stronger in brains with β-amyloid. Stratified analysis shows that the association of APOE ε4 with PHF-tau tangles was considerably stronger among those with β-amyloid (β = 0.757, p = 1.1 × 10(-15)) compared to those without β-amyloid which was not significant (β = -0.201, p = 0.424). Separately, APOE ε2 was associated with fewer tangles in brains with β-amyloid (β = -0.425, p = 7.6 × 10(-4)) compared to those without β-amyloid which was not significant (β = -0.102, p = 0.506). Thus, the presence of APOE ε4 and ε2 alleles was not associated with PHF-tau tangles in the absence of β-amyloid. The data provide additional evidence that PHF-tau tangles in the absence of β-amyloid may reflect a pathologic process distinct from Alzheimer's disease.

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  • Authors+Show Affiliations

    ,

    Department of Geriatrics, University of Sao Paulo Medical School, Sao Paulo, Brazil; Department of Pathology, Rush University Medical Center, Chicago, IL, USA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA. Electronic address: farfel@usp.br.

    ,

    Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.

    ,

    Program in Translational NeuroPsychiatric Genomics, Departments of Neurology and Psychiatry, Institute for the Neurosciences, Brigham and Women's Hospital, Boston, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.

    ,

    Department of Pathology, Rush University Medical Center, Chicago, IL, USA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.

    Department of Geriatrics, University of Sao Paulo Medical School, Sao Paulo, Brazil; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.

    Source

    Neurobiology of aging 37: 2016 Jan pg 19-25

    MeSH

    Aged
    Aged, 80 and over
    Aging
    Alleles
    Alzheimer Disease
    Amyloid beta-Peptides
    Apolipoproteins E
    Brain
    Cohort Studies
    Female
    Genetic Association Studies
    Humans
    Male
    tau Proteins

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural

    Language

    eng

    PubMed ID

    26481403

    Citation

    Farfel, Jose M., et al. "Association of APOE With Tau-tangle Pathology With and Without Β-amyloid." Neurobiology of Aging, vol. 37, 2016, pp. 19-25.
    Farfel JM, Yu L, De Jager PL, et al. Association of APOE with tau-tangle pathology with and without β-amyloid. Neurobiol Aging. 2016;37:19-25.
    Farfel, J. M., Yu, L., De Jager, P. L., Schneider, J. A., & Bennett, D. A. (2016). Association of APOE with tau-tangle pathology with and without β-amyloid. Neurobiology of Aging, 37, pp. 19-25. doi:10.1016/j.neurobiolaging.2015.09.011.
    Farfel JM, et al. Association of APOE With Tau-tangle Pathology With and Without Β-amyloid. Neurobiol Aging. 2016;37:19-25. PubMed PMID: 26481403.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Association of APOE with tau-tangle pathology with and without β-amyloid. AU - Farfel,Jose M, AU - Yu,Lei, AU - De Jager,Philip L, AU - Schneider,Julie A, AU - Bennett,David A, Y1 - 2015/09/28/ PY - 2015/04/08/received PY - 2015/09/08/revised PY - 2015/09/18/accepted PY - 2015/10/21/entrez PY - 2015/10/21/pubmed PY - 2016/9/27/medline KW - Apolipoprotein E KW - Neuropathology KW - Tau-tangle pathology KW - β-amyloid SP - 19 EP - 25 JF - Neurobiology of aging JO - Neurobiol. Aging VL - 37 N2 - This study tested the hypothesis that the association of apolipoprotein E (APOE) with paired helical filament tau (PHF-tau) tangle pathology differs in brains with and without β-amyloid. Participants were 1056 autopsied individuals from 2 clinical-pathologic cohort studies of aging and Alzheimer's disease (AD), the Religious Orders Study, and the Rush Memory and Aging Project. Neuropathologic measures were obtained using immunohistochemistry targeting β-amyloid and PHF-tau tangles in 8 brain regions. Linear regression was used to compare the relation of APOE ε4 and ε2 to PHF-tau-tangle density in persons with β-amyloid relative to persons without β-amyloid. We found an interaction between APOE ε4 carriers and presence of β-amyloid (β = -0.968, p = 0.013) such that the association of APOE ε4 with PHF-tau tangles was much stronger in brains with β-amyloid. Stratified analysis shows that the association of APOE ε4 with PHF-tau tangles was considerably stronger among those with β-amyloid (β = 0.757, p = 1.1 × 10(-15)) compared to those without β-amyloid which was not significant (β = -0.201, p = 0.424). Separately, APOE ε2 was associated with fewer tangles in brains with β-amyloid (β = -0.425, p = 7.6 × 10(-4)) compared to those without β-amyloid which was not significant (β = -0.102, p = 0.506). Thus, the presence of APOE ε4 and ε2 alleles was not associated with PHF-tau tangles in the absence of β-amyloid. The data provide additional evidence that PHF-tau tangles in the absence of β-amyloid may reflect a pathologic process distinct from Alzheimer's disease. SN - 1558-1497 UR - https://www.unboundmedicine.com/medline/citation/26481403/Association_of_APOE_with_tau_tangle_pathology_with_and_without_β_amyloid_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-4580(15)00468-6 DB - PRIME DP - Unbound Medicine ER -