TY  - JOUR
AU  - Finger, Elizabeth
AU  - Malik, Rubina
AU  - Bocchetta, Martina
AU  - Coleman, Kristy
AU  - Graff, Caroline
AU  - Borroni, Barbara
AU  - Masellis, Mario
AU  - Laforce, Robert
AU  - Greaves, Caroline V
AU  - Russell, Lucy L
AU  - Convery, Rhian S
AU  - Bouzigues, Arabella
AU  - Cash, David M
AU  - Otto, Markus
AU  - Synofzik, Matthis
AU  - Rowe, James B
AU  - Galimberti, Daniela
AU  - Tiraboschi, Pietro
AU  - Bartha, Robert
AU  - Shoesmith, Christen
AU  - Tartaglia, Maria Carmela
AU  - van Swieten, John C
AU  - Seelaar, Harro
AU  - Jiskoo, Lize C
AU  - Sorbi, Sandro
AU  - Butler, Chris R
AU  - Gerhard, Alexander
AU  - Sanchez-Valle, Raquel
AU  - de Mendonça, Alexandre
AU  - Moreno, Fermin
AU  - Vandenberghe, Rik
AU  - Le Ber, Isabelle
AU  - Levin, Johannes
AU  - Pasquier, Florence
AU  - Santana, Isabel
AU  - Rohrer, Jonathan D
AU  - Ducharme, Simon
TI  - Neurodevelopmental effects of genetic frontotemporal dementia in young adult mutation carriers
JO  - Brain
VL  - 146
IS  - 5
SN  - 0006-8950
CY  - Oxford
PB  - Oxford Univ. Press
M1  - DZNE-2023-00048
SP  - 2120-2131
PY  - 2023
AB  -  While frontotemporal dementia has been considered a neurodegenerative disease that starts in mid-life or later, it is now clearly established that cortical and subcortical volume loss is observed more than a decade prior to symptom onset and progresses with ageing. To test the hypothesis that genetic mutations causing frontotemporal dementia have neurodevelopmental consequences, we examined the youngest adults in the GENFI cohort of pre-symptomatic frontotemporal dementia mutation carriers who are between 19 and 30 years of age. Structural brain differences and improved performance on some cognitive tests were found for MAPT and GRN mutation carriers relative to familial non-carriers, while smaller volumes were observed in C9orf72 repeat expansion carriers at a mean age of 26 years. The detection of such early differences supports potential advantageous neurodevelopmental consequences of some frontotemporal dementia-causing genetic mutations. These results have implications for the design of therapeutic interventions for frontotemporal dementia. Future studies at younger ages are needed to identify specific early pathophysiologic or compensatory processes that occur during the neurodevelopmental period.
KW  - Humans
KW  - Young Adult
KW  - Adult
KW  - Frontotemporal Dementia: genetics
KW  - Neurodegenerative Diseases
KW  - Progranulins: genetics
KW  - Brain
KW  - Pick Disease of the Brain
KW  - Mutation
KW  - C9orf72 Protein: genetics
KW  - tau Proteins: genetics
KW  - Progranulins (NLM Chemicals)
KW  - C9orf72 (Other)
KW  - GRN (Other)
KW  - MAPT (Other)
KW  - frontotemporal dementia (Other)
KW  - neurodevelopment (Other)
KW  - C9orf72 Protein (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:36458975
DO  - DOI:10.1093/brain/awac446
UR  - https://pub.dzne.de/record/169169
ER  -