title: Synaptophysin and synaptojanin-1 in Down syndrome are differentially affected by Alzheimer's disease.
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.
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Martin
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Amy L S
authors.initials: AL
authors.lastname: Dowling
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Joann
authors.initials: J
authors.lastname: Lianekhammy
authors.affiliation: Department of Physiology, University of Kentucky, Lexington, KY, USA Department of Pediatrics and Neurology, School of Medicine, University of California-Irvine (UCI), Orange, CA, USA.
authors.forename: Ira T
authors.initials: IT
authors.lastname: Lott
authors.affiliation: Department of Physiology, University of Kentucky, Lexington, KY, USA Department of Pediatrics and Neurology, School of Medicine, University of California-Irvine (UCI), Orange, CA, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Doran
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA UK Center for Muscle Biology, University of Kentucky, Lexington, KY, USA.
authors.forename: M Paul
authors.initials: MP
authors.lastname: Murphy
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Tina L
authors.initials: TL
authors.lastname: Beckett
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA Department of Neurology, University of Kentucky, Lexington, KY, USA.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Schmitt
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA Department of Molecular and Biomedical Pharmacology, University of Kentucky, Lexington, KY, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Head
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001344:Autopsy; D001921:Brain / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004314:Down Syndrome / Q000150:complications / Q000473:pathology*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D016708:Synaptophysin / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016229:Amyloid beta-Peptides; D009419:Nerve Tissue Proteins; D016708:Synaptophysin; C097702:synaptojanin; D010744:Phosphoric Monoester Hydrolases
keywords: Amyloid-β; neuroinflammation; oligomers; synapses; synaptojanin; synaptophysin; trisomy 21