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Modulation of Tau Subcellular Localization as a Tool to Investigate the Expression of Disease-related Genes
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Correlations between cortical and subcortical tau pathology.

J Attems1, A Thomas, K Jellinger

  • 1Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK Institute for Clinical Neurobiology, Vienna, Austria. j.attems@ncl.ac.uk

Neuropathology and Applied Neurobiology
|November 26, 2011
PubMed
Summary

Alzheimer's disease (AD) tau pathology increases in the olfactory bulb and brainstem with disease progression, correlating with Braak stages. These regions are increasingly involved during AD, not initially affected.

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Area of Science:

  • Neuroscience
  • Neuropathology
  • Alzheimer's Disease Research

Background:

  • Alzheimer's disease (AD) is characterized by tau pathology.
  • Recent evidence suggests tau pathology may initiate in subcortical regions, not the cerebral cortex.
  • The locus ceruleus (LC) is a key subcortical nucleus implicated in early AD tau spread.

Purpose of the Study:

  • To correlate olfactory bulb (OB) and brainstem tau pathology with neuritic Braak stages in Alzheimer's disease.
  • To investigate the involvement of subcortical nuclei in the progression of tau pathology in AD.
  • To determine if OB and brainstem tau pathology precede or follow cortical involvement in AD.

Main Methods:

  • Examined 239 autopsy cases with varying diagnoses (AD, controls, Parkinson's disease, etc.).
  • Utilized immunohistochemistry and semiquantitative assessment for tau lesions.
  • Assessed tau pathology in the olfactory bulb (OB), locus ceruleus (LC), substantia nigra (SN), and dorsal motor nucleus of the vagus (dmX).

Main Results:

  • Tau pathology was present in the OB (52.9%) and SN/LC (44%) even in Braak stage 0.
  • Prevalence and severity of tau pathology in OB and subcortical nuclei significantly increased with higher Braak stages (P < 0.001).
  • These correlations remained significant when controlling for alpha-synuclein pathology.

Conclusions:

  • Tau pathology in the olfactory bulb and brainstem nuclei (LC, SN, dmX) increases with advancing Braak stages in AD.
  • These findings suggest that these regions are progressively involved during AD, rather than being the initial sites of pathology.
  • The study supports a model where subcortical and olfactory regions are increasingly affected as AD progresses.