title: Functional genetic variation in the serotonin 5-HTTLPR modulates brain damage in frontotemporal dementia.
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.
authors.affiliation: Centre for Ageing Brain and Neurodegenerative Disorders, Neurology Unit, University of Brescia, Brescia, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Premi
authors.affiliation: III Laboratory of Analyses, Brescia Hospital, Brescia, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Archetti
authors.affiliation: Centre for Ageing Brain and Neurodegenerative Disorders, Neurology Unit, University of Brescia, Brescia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pilotto
authors.affiliation: Geriatric Unit and Gerontology-Geriatrics Research Laboratory, Istituto di Ricovero e Cura a Carattere Scientifico, Casa Sollievo della Sofferenza San Giovanni Rotondo, Foggia, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Seripa
authors.affiliation: Nuclear Medicine Unit, University of Brescia, Brescia, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Paghera
authors.affiliation: Centre for Ageing Brain and Neurodegenerative Disorders, Neurology Unit, University of Brescia, Brescia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
authors.affiliation: Centre for Ageing Brain and Neurodegenerative Disorders, Neurology Unit, University of Brescia, Brescia, Italy. Electronic address: bborroni@inwind.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Borroni
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000098:blood supply / Q000473:pathology*; D002560:Cerebrovascular Circulation; D005260:Female; D057180:Frontotemporal Dementia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D059326:Serotonergic Neurons / Q000502:physiology; D012701:Serotonin / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology*; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin
keywords: 5-HTTLPR; Cognitive reserve; Frontotemporal dementia; SLC6A4; SPECT; Serotonin; Statistical parametric mapping