Clinical phenotypes and genetic biomarkers of FTLD

J Neural Transm (Vienna). 2012 Jul;119(7):851-60. doi: 10.1007/s00702-012-0804-0. Epub 2012 Apr 19.

Abstract

Frontotemporal lobar degeneration (FTLD) is the most frequent neurodegenerative disorder with a presenile onset. It presents with a spectrum of clinical manifestations, ranging from behavioural and executive impairment to language disorders and motor dysfunction. New diagnostic criteria identified two main cognitive syndromes: behavioural variant frontotemporal dementia (bvFTD) and primary progressive aphasia (PPA). Regarding bvFTD, new criteria that include the use of biomarkers have been proposed. According to them, bvFTD can be classified in "possible" (clinical features only), "probable" (inclusion of imaging biomarkers) and "definite" (in the presence o f a known causal mutation or at autopsy). Concerning autosomal dominant mutations, microtubule associated protein tau gene mutations have been the first ones identified and are generally associated with early onset bvFTD phenotype. More recently, progranulin gene mutations were recognized in association with familial form of FTLD. In addition, other genes are linked to rare cases of familial FTLD, primarily the newly discovered C9ORF72 hexanucleotide expansion repeats. As regards PPA, new consensus criteria identify three syndromes: primary non-fluent aphasia, semantic variant of PPA and logopenic aphasia, which seems to be associated, in the majority of cases, with underlying Alzheimer's disease pathology. In this review, new criteria, including MRI, cerebrospinal fluid and genetic biomarkers, will be presented and discussed.

Publication types

  • Review

MeSH terms

  • Brain / metabolism*
  • Brain / pathology
  • Frontotemporal Lobar Degeneration / classification
  • Frontotemporal Lobar Degeneration / diagnosis*
  • Frontotemporal Lobar Degeneration / genetics
  • Genetic Markers
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Neuropsychological Tests
  • Phenotype
  • Progranulins
  • tau Proteins / genetics
  • tau Proteins / metabolism

Substances

  • GRN protein, human
  • Genetic Markers
  • Intercellular Signaling Peptides and Proteins
  • MAPT protein, human
  • Progranulins
  • tau Proteins