Caroppo Paola, Habert Marie-Odile, Durrleman Stanley, Funkiewiez Aurélie, Perlbarg Vincent, Hahn Valérie, Bertin Hugo, Gaubert Malo, Routier Alexandre, Hannequin Didier, Deramecourt Vincent, Pasquier Florence, Rivaud-Pechoux Sophie, Vercelletto Martine, Edouart Geoffrey, Valabregue Romain, Lejeune Pascal, Didic Mira, Corvol Jean-Christophe, Benali Habib, Lehericy Stephane, Dubois Bruno, Colliot Olivier, Brice Alexis, Le Ber Isabelle
Sorbonne Universités, UPMC Université Paris 06, UMR S 1127, ICM, Paris, France.
Inserm, U1127, ICM, Paris, France.
J Alzheimers Dis. 2015;47(3):751-9. doi: 10.3233/JAD-150270.
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.
额颞叶变性（FTLD）的临床前期特征尚不明确。我们进行了一项脑代谢（氟代脱氧葡萄糖正电子发射断层扫描，FDG-PET）和结构（皮质厚度）研究，以检测无症状的GRN基因突变携带者（aGRN+）的早期变化，并在20个月的时间里对其进行纵向评估。在基线时，aGRN+存在左侧颞叶低代谢，但无任何结构变化。重要的是，这是第一项纵向研究，随着时间推移，aGRN+的外侧颞叶和额叶区域的代谢下降更快。纵向研究中观察到的主要结构变化是携带者左侧颞叶皮质厚度减少。本研究的一个局限性是样本相对较小（n = 16）；尽管如此，它提供了重要的结果。首先，它证明病理过程在临床发病前很长时间就已发展，并且早期神经影像学变化可能在疾病临床发病前约20年被检测到。其次，它表明代谢变化在结构改变和认知缺陷之前就可被检测到。第三，基线研究和纵向研究都提供了一致的结果，表明外侧颞叶早期参与GRN疾病。最后，我们的研究表明，结构和代谢变化可能代表在症状前期向临床发病阶段监测疾病进展的潜在生物标志物。
