[Abstract Title]. - Society for Neuroscience

Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 244.22/N3
Topic: C.01.b. Abeta assembly and deposition
Support: NIA P50AD16570
NIA 050AG05142
NIH 5AF016570
NIH CA16042
NIH NS43946
Title: Synaptic amyloid beta is elevated in early and mid-stage Alzheimer disease cortex but
decreased in late-stage AD cases
Authors: *K. GYLYS 1 , S. SOKOLOW 1 , K. HENKIINS 1 , C. A. MILLER 3 , H. V. VINTERS 2 ,
G. M. COLE 4 ;
1 Schl Nursing & Brain Res. Inst., 2 Pathology and Lab. Med., UCLA, Los Angeles, CA; 3 Depts of
Pathology, Neurology, and Program in Neurosci., Keck USC Sch. of Med., Los Angeles, CA;
4 Med. and Neurol., UCLA Sch. of Med. and Sepulveda VAMC GRECC, Sepulveda, CA
Abstract: Early cognitive loss correlates with soluble amyloid beta (Aβ) in Alzheimer‟s disease
(AD), and intraneuronal Aβ oligomers are hypothesized to contribute to synaptic dysfunction.
We have developed flow cytometry protocols for quantification of synaptosomal
immunolabeling to characterize and quantify Aβ in synaptic terminals from postmortem AD
cases. Our previous work has demonstrated that synaptic Aβ correlates with oligomers,
colocalizes with p-tau in synaptosomes and is associated with pathological changes (Fein et al.,
2008). Using the 10G4 antibody, we observe striking increases in Aβ immunofluorescence in
AD synaptosomes (mean RFU=122±17, n=19 ) compared to aged normal controls (mean
RFU=32 ±6, n=5). P-tau immunofluorescence using the pS422 antibody is also increased in AD
(mean RFU=54±5, n=19) compared to aged normal controls (mean RFU=31.88±6, n=5).
Synaptic Aβ and p-tau levels in cases with Parkinson‟s disease only (n=2) closely resemble
control cases. Interestingly, two cases with neuropathologically documented tauopathy show
strikingly elevations in synaptic p-tau with the AT100 antibody (mean RFU=129), while p-tau
measured with the pS422 antibody (mean RFU=35.30) resembles the level in controls. A
preliminary analysis of synaptic Aβ level by neuropathologic AD stage shows that synaptic Aβ
level varies significantly with Braak stage (one way ANOVA, p=0.033); stepwise increases are
observed for Braak stages III (mean RFU=115 ±23, n=3) , IV (mean RFU=126 ±44, n=5), and V
(mean RFU=182 ±40, n=5). In late stage cases (Braak stage VI), synaptic Aβ levels decrease
significantly from Stage V levels (mean RFU=87 ±10, n=7, p=.008), but remain higher than in
aged normal controls. Considered together with elevated synaptic Aβ in early to mid-stage AD,