The distribution of phosphorylated tau in spinal cords of Alzheimer's disease and non-demented individuals - PubMed (original) (raw)

Comparative Study

The distribution of phosphorylated tau in spinal cords of Alzheimer's disease and non-demented individuals

Brittany N Dugger et al. J Alzheimers Dis. 2013.

Abstract

Abnormal phosphorylation of the microtubule-associated protein tau develops in selected brain regions in normal aging and becomes widespread throughout the brain in Alzheimer's disease (AD). Braak and others have described the distribution of neurofibrillary tangles and deposition of abnormally phosphorylated tau (p-tau) and correlated this with the progressive cognitive dysfunction in AD. However, to date there have been no comprehensive studies examining abnormally phosphorylated tau deposition in the spinal cord as part of normal aging or AD. We investigated, using immunohistochemical methods, the presence of p-tau in the spinal cord of 46 cases with a clinicopathological diagnosis of AD as well as 37 non-demented aged (ND) individuals lacking any defined central nervous system-related clinicopathological diagnosis. We found the cervical cord segments to be the most frequently affected subdivision (96% AD versus 43% ND), followed by thoracic (69% AD versus 37% ND), lumbar (65% AD versus 27% ND), and sacral (53% AD versus 13% ND). The spinal cord was often affected at early-stage brain disease, with p-tau spinal cord immunoreactivity in 40% of subjects at Braak neurofibrillary stage I; however, there were no cases having spinal cord p-tau that did not have p-tau within the brain. As p-tau immunoreactivity is present within the spinal cords of ND as well as AD subjects, it is likely that the phosphorylation of spinal cord tau occurs in the preclinical stage of AD, prior to dementia. The presence of significant spinal cord p-tau-immunoreactive pathology has important implications for both the pathogenesis and clinical manifestations of AD.

PubMed Disclaimer

Figures

Fig 1

Fig 1

P-tau immunoreactivity in the spinal cord. Ventral part of the cervical horn of a non-demented control (ND) case (a); near the border of ventral horn and intermediolateral region of the lumbar subdivision of an Alzheimer’s disease (AD) case (b); ventral horn of the lumbar subdivision of an AD case (c); intermediolateral region of the lumbar subdivision of an AD case (d); ventral region of the cervical subdivision of an AD case (e); central canal region of the thoracic subdivision of an AD case (f); subpial region of the lumbar subdivision of an AD case (g); and anterior median fissure region of the thoracic subdivision of an AD case (h). Arrows indicate neuropil threads; # indicates neurofibrillary tangles; * indicates pre-tangles; thorned shaped astrocytes are present in (g–h). Insets in a, b, d, g represent higher magnification of small boxed areas. All photos taken at 40x magnification.

Fig 2

Fig 2

Location and densities of all neurites and perikaryal cytoplasmic staining seen across all analyzed Alzheimer’s disease cases at each level of the spinal cord (a). A representation of the typical distribution and density of neurites and perikaryal cytoplasmic staining on 5μm sections of an individual Alzheimer’s disease case at each level of the spinal cord (b). Each neurite is represented by dot while perikaryal cytoplasmic staining by a star.

Fig 3

Fig 3

Prevalence (percentage) of p-tau immunoreactivity in subjects by Braak neurofibrillary stage (a) and spinal cord subdivision (b). Both Alzheimer’s disease and non-demented control subjects are included.

Similar articles

Cited by

References

    1. Hawkes CH, Del Tredici K, Braak H. Parkinson’s disease: a dual-hit hypothesis. Neuropathol Appl Neurobiol. 2007;33:599–614. - PMC - PubMed
    1. Roberts E. Alzheimer’s disease may begin in the nose and may be caused by aluminosilicates. Neurobiol Aging. 1986;7:561–567. - PubMed
    1. Lee JH, Goedert M, Hill WD, Lee VM, Trojanowski JQ. Tau proteins are abnormally expressed in olfactory epithelium of Alzheimer patients and developmentally regulated in human fetal spinal cord. Exp Neurol. 1993;121:93–105. - PubMed
    1. Olanow CW, Prusiner SB. Is Parkinson’s disease a prion disorder? Proc Natl Acad Sci U S A. 2009;106:12571–12572. - PMC - PubMed
    1. Beach TG, Adler CH, Sue LI, Vedders L, Lue L, White CL, III, Akiyama H, Caviness JN, Shill HA, Sabbagh MN, Walker DG. Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders. Acta Neuropathol. 2010;119:689–702. - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources