[Progressive nonfluent aphasia].

Area of Science:

• Neurology
• Pathology
• Neuroscience

Background:

• Frontotemporal lobar degeneration (FTLD) encompasses three clinical phenotypes: progressive nonfluent aphasia (PNFA), semantic dementia (SD), and behavioral variant frontotemporal dementia (bvFTD).
• FTLD classification is based on protein aggregates: tau, TDP-43, and FUS.
• FTLD subtypes have distinct pathological underpinnings, with FTLD-tau and FTLD-TDP-43 further subclassified based on specific protein variants and mutations.

Observation:

• Discrepancies exist in literature regarding the pathological classification of PNFA, with differing inclusions of disorders like corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP).
• While strong correlations are established between semantic dementia and FTLD-TDP-43 type 3, and between certain ALS-dementia types and TDP-43 proteinopathy type 2, such correlations are lacking for PNFA and bvFTD.
• The pathological spectrum of PNFA is broad, potentially including PSP, CBD, Pick's disease, FTDP-17, FTLD-TDP-43 type 3, and even Alzheimer's disease (AD).

Findings:

• Biomarkers such as CSF tau, phosphorylated tau, Aβ, and (11)C-PIB PET scans aid in differentiating Alzheimer's disease from FTLD.
• The diverse pathological background of PNFA complicates direct clinical-pathological correlation compared to other FTD phenotypes.

Implications:

• Establishing clear clinical-pathological correlations for PNFA and bvFTD is crucial for accurate diagnosis and understanding of frontotemporal lobar degeneration.
• Further integrated clinical, radiological, and dynamic neuropathological studies are essential to elucidate the precise pathological underpinnings of PNFA and bvFTD.