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

Paola Caroppo, Marie-Odile Habert, Stanley Durrleman, Aurélie Funkiewiez, Vincent Perlbarg, Valérie Hahn, Hugo Bertin, Malo Gaubert, Alexandre Routier, Didier Hannequin, Vincent Deramecourt, Florence Pasquier, Sophie Rivaud-Pechoux, Martine Vercelletto, Geoffrey Edouart, Romain Valabregue, Pascal Lejeune, Mira Didic, Jean-Christophe Corvol, Habib Benali, Stephane Lehericy, Bruno Dubois, Olivier Colliot, Alexis Brice, Isabelle Le Ber, Predict-PGRN study group, Eric Guedj, Nadine Girard, Christine Rémy, Ali Bouyahia, Marie Chupin, Basile Pinsard, Vanessa Mourlon, Anne De Septenville, Agnès Camuzat, Catherine Thomas-Antérion, Michèle Puel, Jérémie Pariente, Isabelle Berry, Pierre Payoux, Elisabeth Auffray-Calvier, Amandine Pallardy, Adeline Rollin, Christine Delmaire, Franck Semah, Claude Hossein-Foucher, Emmanuel Gerardin, Pierre Vera, Olivier Martinaud, David Wallon, Eric Bardinet, Aurélie Kas, Valérie-Causse Lemercier, Alain Mallet, Merry Masmanian, Sarah Lehoux, Saadane Kirouani, Ivan Mozser, Arthur Tenenhaus, Paola Caroppo, Marie-Odile Habert, Stanley Durrleman, Aurélie Funkiewiez, Vincent Perlbarg, Valérie Hahn, Hugo Bertin, Malo Gaubert, Alexandre Routier, Didier Hannequin, Vincent Deramecourt, Florence Pasquier, Sophie Rivaud-Pechoux, Martine Vercelletto, Geoffrey Edouart, Romain Valabregue, Pascal Lejeune, Mira Didic, Jean-Christophe Corvol, Habib Benali, Stephane Lehericy, Bruno Dubois, Olivier Colliot, Alexis Brice, Isabelle Le Ber, Predict-PGRN study group, Eric Guedj, Nadine Girard, Christine Rémy, Ali Bouyahia, Marie Chupin, Basile Pinsard, Vanessa Mourlon, Anne De Septenville, Agnès Camuzat, Catherine Thomas-Antérion, Michèle Puel, Jérémie Pariente, Isabelle Berry, Pierre Payoux, Elisabeth Auffray-Calvier, Amandine Pallardy, Adeline Rollin, Christine Delmaire, Franck Semah, Claude Hossein-Foucher, Emmanuel Gerardin, Pierre Vera, Olivier Martinaud, David Wallon, Eric Bardinet, Aurélie Kas, Valérie-Causse Lemercier, Alain Mallet, Merry Masmanian, Sarah Lehoux, Saadane Kirouani, Ivan Mozser, Arthur Tenenhaus

Abstract

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.

Keywords: Cortical thickness; GRN; PET; dementia; frontotemporal dementia; frontotemporal lobar degeneration; longitudinal; preclinical study; presymptomatic; progranulin.

Figures

Fig.1
Fig.1
Cluster with significant cortical thickness changes in aGRN+ between the two time-points (p <  0.05 corrected). L, left; R, right.
Fig.2
Fig.2
a) At baseline PET-FDG hypometabolism in aGRN+ compared to GRN- (p <  0.001 uncorrected). L, left; R, right. b) The plot of the adjusted values of [18F]FDG uptake in the cluster is reported. Horizontal line corresponds to the median. GRN−: non carriers, aGRN+: asymptomatic GRN mutation carriers.
Fig.3
Fig.3
Regions of greater percentage of annualized changes of metabolism in aGRN+ compared to GRN− (p <  0.001 uncorrected). L, left; R, right (see Supplementary Table 4 for MNI coordinates and for values).

References

    1. Le Ber I, Camuzat A, Hannequin D, Pasquier F, Guedj E, Rovelet-Lecrux A, Hahn-Barma V, van der Zee J, Clot F, Bakchine S, Puel M, Ghanim M, Lacomblez L, Mikol J, Deramecourt V, Lejeune P, de la Sayette V, Belliard S, Vercelletto M, Meyrignac C, Van Broeckhoven C, Lambert JC, Verpillat P, Campion D, Habert MO, Dubois B, Brice A; French research network on FTD/FTD-MND. Phenotype variability in progranulin mutation carriers: A clinical, neuropsychological, imaging and genetic study. Brain. 2008;131:732–746.
    1. Van Swieten JC, Heutink P. Lancet Neurol. Vol. 7. spectrum; 2008. Mutations in progranulin (GRN) within the of clinical and pathological phenotypes of frontotemporal dementia; pp. 965–974.
    1. Rohrer JD, Lashley T, Schott JM, Warren JE, Mead S, Isaacs AM, Beck J, Hardy J, de Silva R, Warrington E, Troakes C, Al-Sarraj S, King A, Borroni B, Clarkson MJ, Ourselin S, Holton JL, Fox NC, Revesz T, Rossor MN, Warren JD. Clinical and neuroanatomical signatures of tissue pathology in frontotemporal lobar degeneration. Brain. 2011;134:2565–2581.
    1. Whitwell JL, Weigand SD, Boeve BF, Senjem ML, Gunter JL, DeJesus-Hernandez M, Rutherford NJ, Baker M, Knopman DS, Wszolek ZK, Parisi JE, Dickson DW, Petersen RC, Rademakers R, Jack CR Jr, Josephs KA. Neuroimaging signatures of frontotemporal dementia genetics: C9ORF72, tau, progranulin and sporadics. Brain. 2012;135:794–806.
    1. Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, et al. Marcus DS, Cairns NJ, Xie X, Blazey TM, Holtzman DM, Santacruz A, Buckles V, Oliver A, Moulder K, Aisen PS, Ghetti B, Klunk WE, McDade E, Martins RN, Masters CL, Mayeux R, Ringman JM, Rossor MN, Schofield PR, Sperling RA, Salloway S, Morris JC. Dominantly Inherited Alzheimer Network. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med. 2012;367:795–804.
    1. Cenik B, Sephton CF, Dewey CM, Xian X, Wei S, Yu K, Niu W, Coppola G, Coughlin SE, Lee SE, Dries DR, Almeida S, Geschwind DH, Gao FB, Miller BL, Farese RV Jr, Posner BA, Yu G, Herz J. Suberoylanilide hydroxamic acid (vorinostat) up-regulates progranulin transcription: Rational therapeutic approach to frontotemporal dementia. J Biol Chem. 2011;286:16101–16108.
    1. Lee WC, Almeida S, Prudencio M, Caulfield TR, Zhang YJ, Tay WM, Bauer PO, Chew J, Sasaguri H, Jansen-West KR, Gendron TF, Stetler CT, Finch N, Mackenzie IR, Rademakers R, Gao FB, Petrucelli L. Targeted manipulation of the sortilin-progranulin axis rescues progranulin haploinsufficiency. Hum Mol Genet. 2014;23:1467–1478.
    1. Alberici A, Archetti S, Pilotto A, Premi E, Cosseddu M, Bianchetti A, Semeraro F, Salvetti M, Muiesan ML, Padovani A, Borroni B. Results from a pilot study on amiodarone administration in monogenic frontotemporal dementia with granulin mutation. Neurol Sci. 2014;35:1215–1219.
    1. Reuter M, Schmansky NJ, Rosas HD, Fischl B. Within-subject template estimation for unbiased longitudinal image analysis. Neuroimage. 2012;61:1402–1418.
    1. Worbe Y, Gerardin E, Hartmann A, Valabrégue R, Chupin M, Tremblay L, Vidailhet M, Colliot O, Lehéricy S. Distinct structural changes underpin clinical phenotypes in patients with Gilles de la Tourette syndrome. Brain. 2010;133:3649–3660.
    1. Worsley KJ, Andermann M, Koulis T, MacDonald D, Evans AC. Detecting changes in nonisotropic images. Hum Brain Mapp. 1999;8:98–101.
    1. Fouquet M1, Desgranges B, Landeau B, Duchesnay E, Mézenge F, de la Sayette V, Viader F, Baron JC, Eustache F, Chételat G. Longitudinal brain metabolic changes from amnestic mild cognitive impairment to Alzheimer’s disease. Brain. 2009;132:2058–2067.
    1. Mosconi L, Tsui WH, Herholz K, Pupi A, Drzezga A, Lucignani G, Reiman EM, Holthoff V, Kalbe E, Sorbi S, Diehl-Schmid J, Perneczky R, Clerici F, Caselli R, Beuthien-Baumann B, Kurz A, Minoshima S, and de Leon MJ. Multicenter standardized 18F-FDG PET diagnosis of mild cognitive impairment, Alzheimer’s disease, and other dementias. J Nucl Med. 2008;49:390–398.
    1. Whitwell JL, Boeve BF, Weigand SD, Senjem ML, Gunter JL, Baker MC, DeJesus-Hernandez M, Knopman DS, Wszolek ZK, Petersen RC, Rademakers R, Jack CR Jr, Josephs KA. Brain atrophy over time in genetic and sporadic frontotemporal dementia: A study of 198 serial magnetic resonance images. Eur J Neurol. 2015;22:745–752.
    1. Borroni B, Alberici A, Cercignani M, Premi E, Serra L, Cerini C, Cosseddu M, Pettenati C, Turla M, Archetti S, Gasparotti R, Caltagirone C, Padovani A, Bozzali M. Granulin mutation drives brain damage and reorganization from preclinical to symptomatic FTLD. Neurobiol Aging. 2012;33:2506–2520.
    1. Dopper EG, Rombouts SA, Jiskoot LC, den Heijer T, de Graaf JR, de Koning I, Hammerschlag AR, Seelaar H, Seeley WW, Veer IM, van Buchem MA, Rizzu P, van Swieten JC. Structural and functional brain connectivity in presymptomatic familial frontotemporal dementia.e19-e. Neurology. 2014;83:26.
    1. Jacova C, Hsiung GY, Tawankanjanachot I, Dinelle K, McCormick S, Gonzalez M, Lee H, Sengdy P, Bouchard-Kerr P, Baker M, Rademakers R, Sossi V, Stoessl AJ, Feldman HH, Mackenzie IR. Anterior brain glucose hypometabolism predates dementia in progranulin mutation carriers. Neurology. 2013;81:1322–1331.
    1. Moreno F, Sala-Llonch R, Barandiaran M, Sánchez-Valle R, Estanga A, Bartrés-Faz D, Sistiaga A, AlzualdeA, Fernández E, Martí Massó JF, López de Munain A, Indakoetxea B. Distinctive age-relatedtemporal cortical thinning in asymptomatic granulin gene mutation carriers. Neurobiol Aging. 2013;34:1462–1468.
    1. Pievani M, Paternicò D, Benussi L, Binetti G, Orlandini A, Cobelli M, Magnaldi S, Ghidoni R, Frisoni GB. Pattern of structural and functional brain abnormalities in asymptomatic granulin mutation carriers.S354-S363.e. Alzheimers Dement. 2014;10:1.
    1. Premi E, Cauda F, Gasparotti R, Diano M, Archetti S, Padovani A, Borroni B. Multimodal FMRI resting-state functional connectivity in granulin mutations: The case of fronto-parietal dementia.e. PLoS One. 2014;9:106500.
    1. Rohrer JD, Nicholas JM, Cash DM, van Swieten J, Dopper E, Jiskoot L, van Minkelen R, Rombouts SA, Cardoso MJ, Clegg S, Espak M, Mead S, Thomas DL, De Vita E, Masellis M, Black SE, Freedman M, Keren R, MacIntosh BJ, RogaevaE, Tang-Wai D, Tartaglia MC, Laforce R Jr, Tagliavini F, Tiraboschi P, Redaelli V, Prioni S, Grisoli M, BorroniB, Padovani A, Galimberti D, Scarpini E, Arighi A, Fumagalli G, Rowe JB, Coyle-Gilchrist I, Graff C, Fallström M, Jelic V, Ståhlbom AK, Andersson C, Thonberg H, Lilius L, Frisoni GB, Pievani M, Bocchetta M, Benussi L, Ghidoni R, Finger E, Sorbi S, Nacmias B, Lombardi G, Polito C, Warren JD, Ourselin S, Fox NC, RossorMN Presymptomatic cognitive and neuroanatomical changes in genetic frontotemporal dementia in the GeneticFrontotemporal dementia Initiative (GENFI) study: A cross-sectional analysis. Lancet Neurol. 2015;14:253–262.
    1. Dronkers NF, Wilkins DP, Van Valin RD Jr, Redfern BB, Jaeger JJ. Lesion analysis of the brain areas involved in language comprehension. Cognition. 2004;92:145–177.
    1. Ross LA, Olson IR. Social cognition and the anterior temporal lobes. Neuroimage. 2010;49:3452–3462.
    1. Premi E, Garibotto V, Gazzina S, Formenti A, Archetti S, Gasparotti R, Padovani A, Borroni B. Subcortical and deep cortical atrophy in frontotemporal dementia due to granulin mutations. Dement Geriatr Cogn Dis Extra. 2014;4:95–102.
    1. Donovan NJ, Wadsworth LP, Lorius N, Locascio JJ, Rentz DM, Johnson KA, Sperling RA, Marshall GA, AlzheimerDisease Neuroimaging Initiative. Am J Geriatr Psychiatry. Vol. 22. spectrum; 2014. Regional cortical thinning predicts worsening apathy and hallucinationsacross the Alzheimer disease; pp. 1168–1179.
    1. Levy R, Dubois B. Apathy and the functional anatomy of the prefrontal cortex-basal ganglia circuits. Cereb Cortex. 2006;16:916–928.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit