Distinctive pathological mechanisms involved in primary progressive aphasias

Area of Science:

• Neuroscience
• Neuropathology

Background:

• Primary progressive aphasia (PPA) is a group of neurodegenerative diseases with three main cliniconeuroanatomic syndromes.
• Limited data exists on the neuropathologic spread and microscopic changes within each PPA syndrome.

Purpose of the Study:

• To investigate neurodegeneration patterns and quantify microscopic changes in key language brain areas across PPA variants.
• To correlate in vivo imaging findings with postmortem neuropathologic data.

Main Methods:

• Analysis of a longitudinal in vivo cohort and a postmortem PPA cohort.
• Longitudinal analysis of brain atrophy patterns using imaging.
• Quantitative neuropathologic analysis of brain tissue, focusing on neuronal loss and thinning in specific Brodmann areas (BA).

Main Results:

• Semantic variant PPA (sv-PPA) exhibited an eccentric pattern of atrophy, with neuronal loss and thinning in BA 38.
• Nonfluent/agrammatic PPA (nfv-PPA) showed multifocal atrophy extension, thinning in BA 44/45, and microscopic changes in BA 40/22.
• Logopenic PPA (lv-PPA) displayed neuronal loss in BA 40/22 and widespread left-sided brain atrophy on imaging.

Conclusions:

• Each PPA variant demonstrates stereotypical patterns of brain atrophy extension.
• These distinct patterns are largely determined by the underlying specific pathologic type.
• The findings provide insights into the neuropathologic processes driving PPA subtypes.