Lower functional connectivity of default mode network in cognitively normal young adults with mutation of APP, presenilins and APOE ε4
- 404 Downloads
In this study, we used resting-state functional magnetic resonance imaging to explore the genetic effects of amyloid precursor protein (APP) or presenilins mutation and apolipoprotein E (APOE) ε4 on the default-mode network (DMN) in cognitively intact young adults (24.1 ± 2.5 years). Both the APP or presenilin-1/2 group and the APOE ε4 group had significantly lower DMN functional connectivity (FC) in the some brain regions like precuneus/middle cingulate cortices (PCu/MCC) than controls (AlphaSim corrected, P < 0.05). Only a lower FC tendency was demonstrated (control < APOE ε4 < APP or presenilin-1/2 group). Moreover, lower FC in PCu/MCC is correlated with some neuropsychological assessments such as similarity test in APOE ε4 group. These findings indicate that DMN FC alteration in APP or presenilin-1/2 or APOE ε4 subjects is prior to the occurrence of neurological alterations and clinical symptoms, and DMN FC might be a valuable biomarker to detect genetic risk in the preclinical stage.
KeywordsDefault-mode network Apolipoprotein E Amyloid precursor protein Presenilin-1 Presenilin-2 Alzheimer’s disease
amyloid precursor protein
default mode network
middle cingulate cortices
posterior cingulate cortex
resting-state functional MR imaging
Compliance with ethical standards
All procedures performed in studies involving human participants were in accordance with the ethical standards of the local Medical Research Ethics Committee of Jinling Hospital (China).
This study was funded by the grants from Natural Scientific Foundation of China (81,322,020, 81,230,032, and 81,171,313 to L.J.Z.) and Program for New Century Excellent Talents in University (NCET-12-0260 to L.J.Z.).
Competing financial interests
Dr. Schoepf is a consultant for and receives research support from Astellas, Bayer, Bracco, GE, Medrad, and Siemens. The other authors have no conflict of interest to disclose.
- Filippini, N., MacIntosh, B. J., Hough, M. G., Goodwin, G. M., Frisoni, G. B., Smith, S. M., et al. (2009). Distinct patterns of brain activity in young carriers of the APOE-epsilon4 allele. Proceedings of the National Academy of Sciences of the United States of America, 106(17), 7209–7214.CrossRefPubMedPubMedCentralGoogle Scholar
- Fleisher, A. S., Chen, K., Quiroz, Y. T., Jakimovich, L. J., Gomez, M. G., Langois, C. M., et al. (2012). Florbetapir PET analysis of amyloid-beta deposition in the presenilin 1 E280A autosomal dominant Alzheimer's disease kindred: a cross-sectional study. Lancet Neurology, 11(12), 1057–1065.CrossRefPubMedGoogle Scholar
- Fleisher, A. S., Chen, K., Quiroz, Y. T., Jakimovich, L. J., Gutierrez Gomez, M., Langois, C. M., et al. (2015). Associations between biomarkers and age in the presenilin 1 E280A autosomal dominant Alzheimer disease kindred: a cross-sectional study. JAMA Neurol, 72(3), 316–324.CrossRefPubMedPubMedCentralGoogle Scholar
- Fox, M. D., Snyder, A. Z., Vincent, J. L., Corbetta, M., Van Essen, D. C., & Raichle, M. E. (2005). The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proceedings of the National Academy of Sciences of the United States of America, 102(27), 9673–9678.CrossRefPubMedPubMedCentralGoogle Scholar
- Mormino, E. C., Smiljic, A., Hayenga, A. O., Onami, S. H., Greicius, M. D., Rabinovici, G. D., et al. (2011). Relationships between beta-amyloid and functional connectivity in different components of the default mode network in aging. Cerebral Cortex, 21(10), 2399–2407.CrossRefPubMedPubMedCentralGoogle Scholar
- Rami, L., Sala-Llonch, R., Sole-Padulles, C., Fortea, J., Olives, J., Llado, A., et al. (2012). Distinct functional activity of the precuneus and posterior cingulate cortex during encoding in the preclinical stage of Alzheimer's disease. Journal of Alzheimer's Disease, 31(3), 517–526.PubMedGoogle Scholar
- Reiman, E. M., Quiroz, Y. T., Fleisher, A. S., Chen, K., Velez-Pardo, C., Jimenez-Del-Rio, M., et al. (2012). Brain imaging and fluid biomarker analysis in young adults at genetic risk for autosomal dominant Alzheimer's disease in the presenilin 1 E280A kindred: a case-control study. Lancet Neurology, 11(12), 1048–1056.CrossRefPubMedGoogle Scholar
- Shinohara, M., Fujioka, S., Murray, M. E., Wojtas, A., Baker, M., Rovelet-Lecrux, A., et al. (2014). Regional distribution of synaptic markers and APP correlate with distinct clinicopathological features in sporadic and familial Alzheimer's disease. Brain, 137(Pt 5), 1533–1549.CrossRefPubMedPubMedCentralGoogle Scholar