Can neurodegenerative disease be defined by four ‘primary determinants’: anatomy, cells, molecules, and morphology?

Richard A. Armstrong

doi:10.5114/fn.2016.60438

eISSN: 1509-572x
ISSN: 1641-4640

Folia Neuropathologica

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2/2016
vol. 54

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abstract:

Review paper

Can neurodegenerative disease be defined by four ‘primary determinants’: anatomy, cells, molecules, and morphology?

Richard A. Armstrong

Folia Neuropathol 2016; 54 (2): 89-104

DOI: https://doi.org/10.5114/fn.2016.60438

Online publish date: 2016/06/13

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Traditional methods of describing and classifying neurodegenerative disease are based on the clinico-pathological concept supported by molecular pathological studies and defined by ‘consensus criteria’. Disease heterogeneity, overlap between disorders, and the presence of multiple co-pathologies, however, have questioned the validity and status of many traditional disorders. If cases of neurodegenerative disease are not easily classifiable into distinct entities, but more continuously distributed, then a new descriptive framework may be required. This review proposes that there are four key neuropathological features of neurodegenerative disease (the ‘primary determinants’) that could be used to provide such a framework, viz., the anatomical pathways affected by the disease (‘anatomy’), the cell populations affected (‘cells’), the molecular pathology of ‘signature’ pathological lesions (‘molecules’), and the morphological types of neurodegeneration (‘morphology’). This review first discusses the limitations of existing classificatory systems and second provides evidence that the four primary determinants could be used as axes to define all cases of neurodegenerative disease. To illustrate the methodology, the primary determinants were applied to the study of a group of closely related tauopathy cases and to heterogeneity within frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP).

keywords:

Can neurodegenerative disease be defined by four ‘primary determinants’: anatomy, cells, molecules, and morphology?

Richard A. Armstrong

neurodegenerative disease, primary determinants, anatomy, cells, molecules, neurodegeneration