Does apolipoprotein A1 predict microstructural changes in subgenual cingulum in early Parkinson?
Higher plasma cholesterol levels are associated with lower Parkinson’s disease (PD) risk. Apolipoprotein A-1 (ApoA-1) is a surface marker of brain HDL-like particles associated with the time of PD onset. Clinical correlates of serum Apolipoprotein A1 levels with structural brain connectivity in PD-related disorders remains unclear. Here, we applied a novel diffusion-weighted imaging approach [Diffusion Magnetic Resonance Imaging (MRI) Connectometry] to explore the association between ApoA-1 and structural brain connectivity in PD. Participants involved in this research were recruited from Parkinson’s Progression Markers Initiative (PPMI). Diffusion MRI connectometry was conducted using a multiple regression against apoA-1 for 36 patients with DTI measurements available in the baseline visit. Fiber results of the connectometry were then reconstructed for each patient, and diffusion parameters were extracted and regressed against apoA-1 levels. Connectometry results revealed the subgenual cingulum to be associated with ApoA-1, with different FDR yields. This result was further supported by significant negative correlation of Quantitative Anisotropic (QA) of left subgenual cingulum (Pearson’s coefficient = −0.398, p = 0.020) and Generalized Fractional Anisotropic (GFA) of right subgenual cingulum (Pearson’s coefficient −0.457, p = 0.007) with plasma apoA-1 levels, in a multiple regression model with age and sex. The subgenual cingulum encompasses fibers from the anterior cingulate cortex and anterior thalamus. These structures are involved in PD-associated psychosis and executive cognitive decline. We demonstrated for the first time that apoA-1, as a blood marker, can predict microstructural changes in white matter regions in PD patients with undisturbed cognition and mild motor disability.
KeywordsApolipoprotein A1 Subgenual cingulum Early Parkinson’s disease Connectometry Diffusion MRI
This work was funded by Grants from the Michael J Fox Foundation for Parkinson’s Research, the W Garfield Weston Foundation, and the Alzheimer’s Association, the Canadian Institutes for Health Research, and the Natural Sciences and Engineering Research Council of Canada. We thank Christian Beckmann and Simon Eickhoff for their advice on data analysis. Data used in this article were obtained from the Parkinsons Progression Markers Initiative (PPMI) database (http://www.ppmi-info.org/data). For up-to-date information on the study, visit http://www.ppmi-info.org. PPMI is sponsored and partially funded by the Michael J Fox Foundation for Parkinsons Research and funding partners, including AbbVie, Avid Radiopharmaceuticals, Biogen, Bristol-Myers Squibb, Covance, GE Healthcare, Genentech, GlaxoSmithKline (GSK), Eli Lilly and Company, Lundbeck, Merck, Meso Scale Discovery (MSD), Pfizer, Piramal Imaging, Roche, Servier, and UCB (http://www.ppmi-info.org/fundingpartners).
Compliance with ethical standards
All procedures performed here, including human participants, were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
Conflicts of interest
The authors declare that they have no conflict of interest.
- 1.Hottman DA, Chernick D, Cheng S, Wang Z, Li L (2014) HDL and cognition in neurodegenerative disorders. Neurobiology of disease 72 Pt A:22–36. doi: 10.1016/j.nbd.2014.07.015
- 2.Ikeda K, Nakamura Y, Kiyozuka T, Aoyagi J, Hirayama T, Nagata R, Ito H, Iwamoto K, Murata K, Yoshii Y, Kawabe K, Iwasaki Y (2011) Serological profiles of urate, paraoxonase-1, ferritin and lipid in Parkinson’s disease: changes linked to disease progression. Neuro-Degener Dis 8(4):252–258. doi: 10.1159/000323265 CrossRefGoogle Scholar
- 10.Qiang JK, Wong YC, Siderowf A, Hurtig HI, Xie SX, Lee VM, Trojanowski JQ, Yearout D, Leverenz JB, Montine TJ, Stern M, Mendick S, Jennings D, Zabetian C, Marek K, Chen-Plotkin AS (2013) Plasma apolipoprotein A1 as a biomarker for Parkinson disease. Ann Neurol 74(1):119–127. doi: 10.1002/ana.23872 CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Jones DK, Christiansen KF, Chapman RJ, Aggleton JP (2013) Distinct subdivisions of the cingulum bundle revealed by diffusion MRI fibre tracking: implications for neuropsychological investigations. Neuropsychologia 51(1):67–78. doi: 10.1016/j.neuropsychologia.2012.11.018 CrossRefPubMedPubMedCentralGoogle Scholar
- 14.Martinez-Martin P, Rodriguez-Blazquez C, Mario A, Arakaki T, Arillo VC, Chana P, Fernandez W, Garretto N, Martinez-Castrillo JC, Rodriguez-Violante M, Serrano-Duenas M, Ballesteros D, Rojo-Abuin JM, Chaudhuri KR, Merello M (2015) Parkinson’s disease severity levels and MDS-Unified Parkinson’s Disease Rating Scale. Parkinsonism Relat Disord 21(1):50–54. doi: 10.1016/j.parkreldis.2014.10.026 CrossRefPubMedGoogle Scholar
- 19.Nigro S, Riccelli R, Passamonti L, Arabia G, Morelli M, Nistico R, Novellino F, Salsone M, Barbagallo G, Quattrone A (2016) Characterizing structural neural networks in de novo Parkinson disease patients using diffusion tensor imaging. Hum Brain Mapp 37(12):4500–4510. doi: 10.1002/hbm.23324 CrossRefPubMedGoogle Scholar
- 20.Ansari M, Rahmani F, Dolatshahi M, Pooyan A, Aarabi MH (2016) Brain pathway differences between Parkinson’s disease patients with and without REM sleep behavior disorder. Sleep Breathing Schlaf Atmung. doi: 10.1007/s11325-016-1435-8
- 21.Rahmani F, Ansari M, Pooyan A, Mirbagheri MM, Aarabi MH (eds) (2016) Differences in white matter microstructure between Parkinson's disease patients with and without REM sleep behavior disorder. In: Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS Google Scholar
- 23.Huebl J, Brucke C, Merkl A, Bajbouj M, Schneider GH, Kuhn AA (2016) Processing of emotional stimuli is reflected by modulations of beta band activity in the subgenual anterior cingulate cortex in patients with treatment resistant depression. Soc Cogn Affect Neurosci 11(8):1290–1298. doi: 10.1093/scan/nsw038 CrossRefPubMedGoogle Scholar
- 24.Keedwell PA, Doidge AN, Meyer M, Lawrence N, Lawrence AD, Jones DK (2016) Subgenual cingulum microstructure supports control of emotional conflict. Cereb Cortex (New York, NY: 1991) 26(6):2850–2862. doi: 10.1093/cercor/bhw030
- 40.Mole JP, Subramanian L, Bracht T, Morris H, Metzler-Baddeley C, Linden DE (2016) Increased fractional anisotropy in the motor tracts of Parkinson’s disease suggests compensatory neuroplasticity or selective neurodegeneration. Eur Radiol. doi: 10.1007/s00330-015-4178-1 PubMedPubMedCentralGoogle Scholar