Epidemiology

• Age of onset: usually between 40 and 60 years (typically younger than in Alzheimer disease)

Etiology

• Generally associated with pathological intracellular inclusion bodies (Pick bodies) that are caused by mutations in tau (main protein component of Pick bodies) or progranulin (precursor of granulin, which regulates cell growth) proteins

Pathophysiology

Clinical features

• Early changes in personality and behavior → inability to observe social etiquette
  • Apathy
  • Disinhibited behavior
    • A pattern of socially inappropriate and often impulsive behavior that is seen in several neurological disorders
    • Examples include offensive language and inappropriate touching.
• Changes in cognitive functioning
  • Aphasia (but no apraxia)
  • Intelligence, orientation, and memory initially intact
• Motor deficits
  • Parkinsonism (in later stages)

Diagnostics

Pathology

• Detection of different types of intracellular inclusions in surviving neurons (tau or TDP-43 in approx. 90% of cases)
  • Pick bodies (FTLD-tau): round cytoplasmic inclusions of aggregated hyperphosphorylated tau proteins
  • FTLD‑TDP: inclusions with ubiquitinated TDP‑43

Treatment