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A Practical Approach to Differentiate the Frontotemporal Tauopathy Subtypes.

Shelley L Forrest¹, Glenda M Halliday^2,3,4, Anastasia Sizemova¹

¹Discipline of Pathology, School of Medical Sciences.

Journal of Neuropathology and Experimental Neurology

|September 21, 2020

Summary

This study presents a simplified method for classifying frontotemporal lobar degeneration with tau-immunopositive inclusions (FTLD-tau) subtypes. The approach uses minimal brain regions and stains, achieving high interrater reliability for accurate neuropathological diagnosis.

Keywords:

Frontotemporal lobar degeneration Pathological classification Tau

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Area of Science:

Neuroscience
Neuropathology
Biomarker Discovery

Background:

Frontotemporal lobar degeneration with tau-immunopositive inclusions (FTLD-tau) encompasses diverse subtypes.
Accurate neuropathological classification is crucial for understanding disease mechanisms and progression.
Existing criteria for FTLD-tau subtyping can be complex and require consolidation.

Purpose of the Study:

To develop and validate an operationalized schema for differentiating FTLD-tau subtypes.
To consolidate existing neuropathological criteria into a practical diagnostic approach.
To assess the interrater reliability of the proposed schema.

Main Methods:

Utilized specific brain regions (superior frontal cortex, precentral cortex, hippocampus, midbrain) and stains (phosphorylated-tau, p62, modified Bielschowsky silver).
Evaluated 24 FTLD-tau cases, including Pick disease, corticobasal degeneration, progressive supranuclear palsy, and globular glial tauopathy.
Assessed interrater reliability among 10 independent observers using the developed schema.

Main Results:

The proposed approach demonstrated high accuracy in differentiating FTLD-tau subtypes.
All assessed brain regions and stains were informative for pathological subtyping.
Independent observers achieved almost perfect agreement in classifying cases, highlighting the schema's effectiveness.

Conclusions:

The study provides an efficient, simple, and accurate method for FTLD-tau subtyping.
The operationalized schema consolidates current diagnostic criteria for future clinicopathological studies.
Identifying subtype-specific neuropathological features is essential for accurate FTLD-tau classification.