Lateral Temporal Lobe: An Early Imaging Marker of the Presymptomatic GRN Disease?

Paola Caroppo (1) , Marie-Odile Habert (2) , Stanley Durrleman (3) , Aurélie Funkiewiez (4) , Vincent Perlbarg (5) , Valérie Hahn (6) , Hugo Bertin (7, 8) , Malo Gaubert (9) , Alexandre Routier (3) , Didier Hannequin (10) , Vincent Deramecourt (11) , Florence Pasquier (11) , Sophie Rivaud-Pechoux (12) , Martine Vercelletto (13) , Geoffrey Edouart (6) , Romain Valabregue (14) , Pascal Lejeune (6) , Mira Didic (6) , Jean-Christophe Corvol (14) , Habib Benali (2) , Stéphane Lehéricy (14) , Bruno Dubois (6) , Olivier Colliot (3) , Alexis Brice (14) , Isabelle Le Ber (1, 15)

1 CRICM - Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière
2 LIB - Laboratoire d'Imagerie Biomédicale [Paris]
3 ARAMIS - Algorithms, models and methods for images and signals of the human brain = Algorithmes, modèles et méthodes pour les images et les signaux du cerveau humain [ICM Paris]
4 Neurosciences précliniques
5 LIF - Laboratoire d'Imagerie Fonctionnelle
6 IM2A - Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre]
7 TREFLE - Transferts, écoulements, fluides, énergétique
8 I2M - Institut de Mécanique et d'Ingénierie de Bordeaux
9 LOV - Laboratoire d'océanographie de Villefranche
10 GMFC - Génétique du cancer et des maladies neuropsychiatriques
11 TCDV - Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046
12 Neurologie et thérapeutique expérimentale
13 Service de neurologie [Nantes]
14 ICM - Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute
15 CHU Pitié-Salpêtrière [AP-HP]

The preclinical stage of frontotemporal lobar degeneration (FTLD) is not well characterized. We conducted a brain metabolism (FDG-PET) and structural (cortical thickness) study to detect early changes in asymptomatic GRN mutation carriers (aGRN+) that were evaluated longitudinally over a 20-month period. At baseline, a left lateral temporal lobe hypometabolism was present in aGRN+ without any structural changes. Importantly, this is the first longitudinal study and, across time, the metabolism more rapidly decreased in aGRN+ in lateral temporal and frontal regions. The main structural change observed in the longitudinal study was a reduction of cortical thickness in the left lateral temporal lobe in carriers. A limit of this study is the relatively small sample (n = 16); nevertheless, it provides important results. First, it evidences that the pathological processes develop a long time before clinical onset, and that early neuroimaging changes might be detected approximately 20 years before the clinical onset of disease. Second, it suggests that metabolic changes are detectable before structural modifications and cognitive deficits. Third, both the baseline and longitudinal studies provide converging results implicating lateral temporal lobe as early involved in GRN disease. Finally, our study demonstrates that structural and metabolic changes could represent possible biomarkers to monitor the progression of disease in the presymptomatic stage toward clinical onset.

Mots clés: frontotemporal lobar degeneration; frontotemporal dementia; dementia; PET; preclinical study; longitudinal; Cortical thickness; GRN; presymptomatic; progranulin

Domaines: Traitement du signal et de l'image [eess.SP]; Neurobiologie

Paola Caroppo, Marie-Odile Habert, Stanley Durrleman, Aurélie Funkiewiez, Vincent Perlbarg, et al.. Lateral Temporal Lobe: An Early Imaging Marker of the Presymptomatic GRN Disease?. Journal of Alzheimer's Disease, 2015, 47 (3), pp.751-9. ⟨10.3233/JAD-150270⟩. ⟨hal-01220380⟩