Neurotransmitter deficits from frontotemporal lobar degeneration

Brain. 2018 May 1;141(5):1263-1285. doi: 10.1093/brain/awx327.


Frontotemporal lobar degeneration causes a spectrum of complex degenerative disorders including frontotemporal dementia, progressive supranuclear palsy and corticobasal syndrome, each of which is associated with changes in the principal neurotransmitter systems. We review the evidence for these neurochemical changes and propose that they contribute to symptomatology of frontotemporal lobar degeneration, over and above neuronal loss and atrophy. Despite the development of disease-modifying therapies, aiming to slow neuropathological progression, it remains important to advance symptomatic treatments to reduce the disease burden and improve patients' and carers' quality of life. We propose that targeting the selective deficiencies in neurotransmitter systems, including dopamine, noradrenaline, serotonin, acetylcholine, glutamate and gamma-aminobutyric acid is an important strategy towards this goal. We summarize the current evidence-base for pharmacological treatments and suggest strategies to improve the development of new, effective pharmacological treatments.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Frontotemporal Lobar Degeneration / drug therapy
  • Frontotemporal Lobar Degeneration / metabolism*
  • Humans
  • Neurotransmitter Agents / deficiency*
  • Neurotransmitter Agents / therapeutic use


  • Neurotransmitter Agents