CSF sulfatide is decreased in individuals with incipient
dementia
Xianlin Han, PhD, Anne M. Fagan, PhD, Hua Cheng, MS, John C. Morris, MD,
Chengjie Xiong, PhD, David M. Holtzman, MD
Washington University School of Medicine
Department of Medicine and Neurology
Pro
gres
sion
Time
Cognitive Function
Pre-clinical Very MildCDR 0.5 MCI
Clinical detection threshold
MildCDR1
Stage of dementia
Moderate
Severe
AD pathological burden
Onset of AD pathology
An unbiased screen of normal and AD brain tissue using ESI-mass spectrometry led to identification of marked decline in sulfatide in both gray and white matter at CDR 0.5 level of dementia due to AD. *Most other lipids were unchanged.
Han et al. J. Neurochem. 2002
Sulfatide: a sulfated galactocerebroside* synthesized by oligodendrocytes* buildup due to sulfatidase deficiency causes metachromatic leukodystrophy* present in lipoprotein particles along with apoE in the CNS
Electrospray ionization mass spectrometry: Decrease in sulfatidesin very mild AD frontal grey matter vs. control
CDR 0 CDR 0.5 p-value Subjects N=19 N=20 Male/Female 9/10 5/15 % Caucasian 95% 95% Age 70.6 +/- 1.3 73.9 +/- 1.7 0.12 Years of Education 14.21 +/- 0.71 15.1 +/- 0.82 0.44 MMSE score 29.4 +/- 0.18 26.4 +/-0.72 0.0002 Table 1. Characteristics of study subjects. (Mean +/- SEM)
Characteristics of initial group in CSF study
All CSF and plasma was collected fasting at 8AMSamples were stored at –70oC till analyzed
0
25
50
75
100
CDR 0 CDR 0.5
Su
lfat
ide
(pm
ol/
ml)
0
50
100
150
CDR 0 CDR 0.5
ph
osp
hat
idyl
ino
sito
l (P
I)pm
ol/m
l
CSF sulfatide (ST) is markedly and significantly lower inCDR 0.5 vs. CDR 0 subjects
0
5
10
15
20
25
30
CDR 0 CDR 0.5
MM
SE
sco
re
0.0
0.5
1.0
1.5
CDR 0 CDR 0.5
Su
lfat
ide/
PI
rati
o
0
500
1000
1500
CDR 0 CDR 0.5
A
42 (
pg
/ml)
0
1000
2000
3000
CDR 0 CDR 0.5
Tau
pro
tein
(p
g/m
l)Sensitivity and specificity of CSF sulfatide/PI ratio in differentiating CDR 0 from CDR 0.5 subjects is better in thissample than several other established AD biomarkers
Sens=90%Spec=100%
0
100
200
CDR 0 CDR 0.5
pT
au18
1P (
pg
/ml)
Future Questions to be addressed
1. Does sulfatide or the ST/PI ratio differentiate subjects who have a CDR score of 0 from a score of 0.5 and greater in other samples?
2. Are there storage or collection issues that are critical in assessment of this CSF biomarker?
3. Does a low ST/PI ratio increase risk of converting from CDR 0 to CDR 0.5 or from CDR 0.5 to 1?
4. Is a decrease in ST/PI ratio specific for AD vs. other neuro-degenerative diseases (e.g. Parkinson’s, fronto-temporal dementia, etc.).
control-ST AD-ST0
10
20
30
40 *
p<0.0001
CSF Sulfatide
ST
pm
ol/
ml
control: N=33AD: N=46
CSF sulfatide is decreased in a large sample of AD vs. controls subjects
(samples from Joseph Quinn, MD, PhD, Oregon Health Sciences)
Top Related