Plasma amyloid beta protein is elevated in late-onset Alzheimer disease families.
OBJECTIVE
Plasma A beta levels are elevated in early-onset Alzheimer disease (AD) caused by autosomal dominant mutations. Our objective was to determine whether similar genetic elevations exist in late-onset AD (LOAD).


METHODS
We measured plasma A beta in first-degree relatives of patients with LOAD in a cross-sectional series and in extended LOAD families. We screened these subjects for pathogenic mutations in early-onset AD genes and determined their ApoE genotypes.


RESULTS
Plasma A beta is significantly elevated in the LOAD first-degree relatives in comparison to unrelated controls and married-in spouses. These elevations are not due to ApoE epsilon 4 or pathogenic coding mutations in the known early-onset AD genes.


CONCLUSIONS
The findings provide strong evidence for the existence of novel, as yet unknown genetic factors that affect late-onset Alzheimer disease by increasing A beta.
Ertekin-Taner
N
N
Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL 32224, USA.
Younkin
L H
LH
Yager
D M
DM
Parfitt
F
F
Baker
M C
MC
Asthana
S
S
Hutton
M L
ML
Younkin
S G
SG
Graff-Radford
N R
NR
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000097:blood*; D053327:Apolipoprotein E4 / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011110:Polymorphism, Genetic; D053763:Presenilins / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D012737:Sex Factors; D013997:Time Factors
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D010446:Peptide Fragments; D053763:Presenilins; C075222:amyloid beta-protein (1-42)