The effects of normal aging and ApoE genotype on the levels of CSF biomarkers for Alzheimer's disease.
While cerebrospinal fluid (CSF) biomarkers are of use in the prediction and diagnosis of Alzheimer's disease our understanding of the background effects of age and the ApoE genotype is limited. Seventy-eight community-based normal volunteers (mean age 60+/-10 years, range 36-86) were examined to determine the relationships between CSF measures of total tau (T-tau), hyperphosphorylated tau (P-tau 231), amyloid beta (Abeta42/Abeta40 ratio), and isoprostane (IP) with age and ApoE genotype. The results showed that age by epsilon4 genotype interactions were found for P-tau231 (beta=1.82; p<0.05) and IP (beta=1.6; p<0.05). T-tau CSF concentration increased with age. The increasing CSF concentrations of P-tau and IP in epsilon4 carriers suggest that early tauopathy and oxidative stress may be related to the increased risk for AD. The data also suggest that T-tau changes are more age dependent than Abeta changes. The evidence that P-tau231 and IP are the earliest markers for the neuronal damage related to AD awaits longitudinal study.
Glodzik-Sobanska
Lidia
L
New York University School of Medicine, New York, NY 10016, United States.
Pirraglia
Elizabeth
E
Brys
Miroslaw
M
de Santi
Susan
S
Mosconi
Lisa
L
Rich
Kenneth E
KE
Switalski
Remigiusz
R
Saint Louis
Leslie
L
Sadowski
Martin J
MJ
Martiniuk
Frank
F
Mehta
Pankaj
P
Pratico
Domenico
D
Zinkowski
Raymond P
RP
Blennow
Kaj
K
de Leon
Mony J
MJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000134:cerebrospinal fluid; D053327:Apolipoprotein E4 / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D015415:Biomarkers / Q000032:analysis / Q000134:cerebrospinal fluid; D004252:DNA Mutational Analysis; D015237:Dinoprost / Q000031:analogs & derivatives / Q000032:analysis / Q000134:cerebrospinal fluid; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics; D010446:Peptide Fragments / Q000032:analysis / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D011110:Polymorphism, Genetic / Q000235:genetics; D016875:tau Proteins / Q000032:analysis / Q000134:cerebrospinal fluid
C115626:8,12-iso-isoprostane F2alpha-VI; D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D015415:Biomarkers; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D015237:Dinoprost