Synaptophysin and Synaptojanin-1 in Down Syndrome are Differentially Affected by Alzheimer's Disease

Article type: Research Article

Authors: Martin, Sarah B.^a | Dowling, Amy L.S.^a | Lianekhammy, Joann^a | Lott, Ira T.^{f; g} | Doran, Eric^{f; g} | Murphy, M. Paul^{a; d; e} | Beckett, Tina L.^a | Schmitt, Frederick A.^{a; b} | Head, Elizabeth^{a; c; *}

Affiliations: [a] Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA | [b] Department of Neurology, University of Kentucky, Lexington, KY, USA | [c] Department of Molecular and Biomedical Pharmacology, University of Kentucky, Lexington, KY, USA | [d] Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA | [e] UK Center for Muscle Biology, University of Kentucky, Lexington, KY, USA | [f] Department of Physiology, University of Kentucky, Lexington, KY, USA | [g] Department of Pediatrics and Neurology, School of Medicine, University of California-Irvine (UCI), Orange, CA, USA

Correspondence: [*] Correspondence to: Elizabeth Head, MA, PhD, Sanders Brown Center on Aging, Department of Molecular and Biomedical Pharmacology, University of Kentucky, 203 Sanders-Brown Building, 800 South Limestone Street, Lexington, KY 40536-0230, USA. Tel.: +1 859 218 3172; Fax: +1 859 323 2866; E-mail: elizabeth.head@uky.edu.

Abstract: Adults with Down syndrome (DS) develop Alzheimer's disease (AD) neuropathology by 40 years of age. Synaptophysin (SYN) consistently declines with age and is further reduced with sporadic AD. Thus, we hypothesized that SYN would be reduced in DS with AD. The gene for synaptojanin-1 (SYNJ1), involved in synaptic vesicle recycling, is on chromosome 21. We measured SYN and SYNJ1 in an autopsy series of 39 cases with DS and 28 without DS, along with 7 sporadic AD cases. SYN was significantly lower in DSAD compared with DS alone and similar to sporadic AD. Reduced SYN is associated with AD neuropathology and with Aβ levels in DS, as is seen in sporadic AD. SYNJ1 was significantly higher in DS and correlated with several measures of Aβ. SYNJ1 was higher in DSAD and significantly higher than SYNJ1 in sporadic AD. Although significantly higher in DS, SYNJ1 is further increased with AD neuropathology suggesting interesting differences in a synapse-associated protein that is overexpressed in trisomy 21.

Keywords: Amyloid-β, neuroinflammation, oligomers, synapses, synaptojanin, synaptophysin, trisomy 21

DOI: 10.3233/JAD-140795

Journal: Journal of Alzheimer's Disease, vol. 42, no. 3, pp. 767-775, 2014