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This study mapped proteinopathy deposition in the medial temporal lobe (MTL). Hyperphosphorylated tau (p-tau) and TDP-43 show distinct patterns, informing neuroimaging biomarker development for dementia.

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Area of Science:

  • Neuroscience
  • Neuropathology
  • Biomarker Discovery

Background:

  • The medial temporal lobe (MTL) is crucial for memory and frequently affected in dementia.
  • Understanding proteinopathy deposition in the MTL is vital for interpreting neuroimaging findings.
  • Six major proteinopathies targeting the MTL were investigated.

Purpose of the Study:

  • To quantitatively characterize the deposition patterns of six major proteinopathies within MTL subregions.
  • To harmonize and compare pathology measures across diverse studies.
  • To inform the interpretation of neuroimaging data and guide biomarker development.

Main Methods:

  • A comprehensive literature review of 99 publications was conducted.
  • Medial temporal lobe (MTL) pathology measures were normalized to a 0-5 scale.
  • Average pathology ratings were calculated per MTL subregion, proteinopathy, and clinical diagnosis, weighted by sample size.

Main Results:

  • Hyperphosphorylated tau (p-tau) showed highest deposition in the transentorhinal cortex (TERC), entorhinal cortex (ERC), CA1, and subiculum.
  • TDP-43 and argyrophilic grains exhibited similar patterns, predominantly in the amygdala and ERC.
  • Pick bodies were most concentrated in the dentate gyrus and amygdala; alpha-synuclein and amyloid-beta in the lateral MTL cortex and amygdala.

Conclusions:

  • Proteinopathies like p-tau, TDP-43, and argyrophilic grains share deposition patterns in MTL subregions.
  • Other proteinopathies display unique vulnerabilities within specific MTL subregions.
  • Identified patterns can guide the development of sensitive and specific neuroimaging biomarkers for heterogeneous proteinopathies.