[Pick's disease: clinicopathological features for antemortem diagnosis]

Area of Science:

• Neuroscience
• Neuropathology
• Clinical Neurology

Background:

• Frontotemporal lobar degeneration (FTLD) encompasses major subtypes including FTLD with ubiquitin/TDP-43-positive inclusions (FTLD-TDP) and Pick's disease.
• Accurate in-vivo pathological diagnosis is crucial for developing targeted treatments for sporadic FTLD.
• Current clinical data are insufficient for precise pathological subtyping during a patient's lifetime.

Purpose of the Study:

• To explore clinicopathological differences between sporadic FTLD-TDP and Pick's disease.
• To investigate how clinical presentations of FTLD-TDP with progranulin gene (PGRN) mutations compare to sporadic FTLD-TDP and Pick's disease.
• To highlight the need for clinical data to differentiate FTLD subtypes beyond Alzheimer's disease.

Main Methods:

• Review of recent and previous studies on clinical presentations of FTLD subtypes.
• Comparison of syndromic onset (frontotemporal dementia, progressive non-fluent aphasia, semantic dementia) across pathologies.
• Analysis of the frequency of asymmetric motor disturbances in different FTLD subtypes.

Main Results:

• Pick's disease often presents initially with frontotemporal dementia or progressive non-fluent aphasia.
• Sporadic FTLD-TDP cases frequently exhibit semantic dementia as the initial syndrome.
• Asymmetric motor disturbances are common in sporadic FTLD-TDP but rare in Pick's disease.

Conclusions:

• Clinicopathological features of sporadic FTLD-TDP appear distinct from Pick's disease and FTLD-TDP with PGRN mutations.
• Understanding these differences is vital for future clinical differentiation of FTLD subtypes.
• Advancements in in-vivo imaging necessitate better clinical data for distinguishing FTLD pathologies.