Functional genetic variation in the serotonin 5-HTTLPR modulates brain damage in frontotemporal dementia

Enrico Premi, Silvana Archetti, Andrea Pilotto, Davide Seripa, Barbara Paghera, Alessandro Padovani, Barbara Borroni

Research output: Contribution to journalArticlepeer-review

Abstract

In frontotemporal dementia (FTD), nonmodifiable (genetic background) and modifiable (cognitive reserve [CR]) factors might interact in affecting frontotemporal damage. Serotoninergic dysfunction has been suggested as a key factor in FTD pathogenesis. 5-HTTLPR polymorphism on SCLA4 gene modulates the serotoninergic transmission. To evaluate the impact of 5-HTTLPR polymorphism on regional cerebral blood flow (rCBF) and its possible interaction with CR, 76 FTD patients with a 5-HTTLPR genotyping were recruited. All subjects underwent neuropsychological assessment and single-photon emission computed tomography imaging. Reserve index (RI) was computed from educational and occupational attainments, as proxy measure of CR. 5-HTTLPR analysis evidenced 14 S/S, 24 L/L, and 38 S/L carriers. No neuropsychological/behavioral differences were present. At the same disease stage, L/L carriers have a greater bilateral frontal rCBF decrease. Patients with higher RI had greater damage in right frontal and temporal regions. The additive effect of 5-HTTLPR polymorphism and RI was characterized by greater frontal rCBF deficit. 5-HTTLPR and CR act together to counteract brain pathology in FTD. Further studies are warranted to test the serotonin role in monogenic forms of FTD.

Original languageEnglish
Pages (from-to)446-451
Number of pages6
JournalNeurobiology of Aging
Volume36
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

Keywords

  • 5-HTTLPR
  • Cognitive reserve
  • Frontotemporal dementia
  • Serotonin
  • SLC6A4
  • SPECT
  • Statistical parametric mapping

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology
  • Medicine(all)

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