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A 2-process model for neuropathology of Alzheimer's disease.

Abstract

This study examined relations among neuritic and diffuse plaques, neurofibrillary tangles, age, and apolipoprotein E (APOE) in 2 large samples of neuropathology cases, the Religious Orders Study and the Memory and Aging Project. Cognitive status ranged from normal to demented and AD neuropathology ranged from none to severe. Confirmatory factor analysis identified a best-fitting 4-factor solution to describe interrelationships among plaques and tangles: a global neuritic plaque factor; a global diffuse plaque factor; a factor defined by medial temporal neurofibrillary tangles; and a neocortical tangle factor. Results supported a hypothesis that neuritic plaques mediate the association of age and APOE with neocortical tangles, and similarly mediate the effect of APOE on medial temporal tangles. However, medial temporal tangles were related to age independent of neuritic plaques. These results support a primary amyloid-based AD process that accounts for neocortical tangles and makes the largest contribution to medial temporal tangles. A second, age-related but non-amyloid process likely contributes to medial temporal lobe tangles.

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  • Authors+Show Affiliations

    ,

    Department of Neurology, School of Medicine, University of California, Davis, CA, USA. Electronic address: dmmungas@ucdavis.edu.

    , , ,

    Source

    Neurobiology of aging 35:2 2014 Feb pg 301-8

    MeSH

    Aged
    Aged, 80 and over
    Aging
    Alzheimer Disease
    Apolipoproteins E
    Brain
    Cohort Studies
    Female
    Humans
    Male
    Middle Aged
    Models, Statistical
    Neurofibrillary Tangles
    Plaque, Amyloid
    Prospective Studies
    Risk Factors

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    24080173

    Citation

    Mungas, Dan, et al. "A 2-process Model for Neuropathology of Alzheimer's Disease." Neurobiology of Aging, vol. 35, no. 2, 2014, pp. 301-8.
    Mungas D, Tractenberg R, Schneider JA, et al. A 2-process model for neuropathology of Alzheimer's disease. Neurobiol Aging. 2014;35(2):301-8.
    Mungas, D., Tractenberg, R., Schneider, J. A., Crane, P. K., & Bennett, D. A. (2014). A 2-process model for neuropathology of Alzheimer's disease. Neurobiology of Aging, 35(2), pp. 301-8. doi:10.1016/j.neurobiolaging.2013.08.007.
    Mungas D, et al. A 2-process Model for Neuropathology of Alzheimer's Disease. Neurobiol Aging. 2014;35(2):301-8. PubMed PMID: 24080173.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - A 2-process model for neuropathology of Alzheimer's disease. AU - Mungas,Dan, AU - Tractenberg,Rochelle, AU - Schneider,Julie A, AU - Crane,Paul K, AU - Bennett,David A, Y1 - 2013/09/27/ PY - 2013/01/26/received PY - 2013/08/07/revised PY - 2013/08/10/accepted PY - 2013/10/2/entrez PY - 2013/10/2/pubmed PY - 2014/8/26/medline KW - APOE KW - Age KW - Alzheimer's disease KW - Latent variable modeling KW - Neuropathology SP - 301 EP - 8 JF - Neurobiology of aging JO - Neurobiol. Aging VL - 35 IS - 2 N2 - This study examined relations among neuritic and diffuse plaques, neurofibrillary tangles, age, and apolipoprotein E (APOE) in 2 large samples of neuropathology cases, the Religious Orders Study and the Memory and Aging Project. Cognitive status ranged from normal to demented and AD neuropathology ranged from none to severe. Confirmatory factor analysis identified a best-fitting 4-factor solution to describe interrelationships among plaques and tangles: a global neuritic plaque factor; a global diffuse plaque factor; a factor defined by medial temporal neurofibrillary tangles; and a neocortical tangle factor. Results supported a hypothesis that neuritic plaques mediate the association of age and APOE with neocortical tangles, and similarly mediate the effect of APOE on medial temporal tangles. However, medial temporal tangles were related to age independent of neuritic plaques. These results support a primary amyloid-based AD process that accounts for neocortical tangles and makes the largest contribution to medial temporal tangles. A second, age-related but non-amyloid process likely contributes to medial temporal lobe tangles. SN - 1558-1497 UR - https://www.unboundmedicine.com/medline/citation/24080173/A_2_process_model_for_neuropathology_of_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-4580(13)00341-2 DB - PRIME DP - Unbound Medicine ER -