CSF tau/Abeta42 ratio for increased risk of mild cognitive impairment: a follow-up study.
BACKGROUND
Processes of Alzheimer disease (AD) likely begin years prior to the onset of cognitive impairment (latent AD), progress though a prodromal phase of mild cognitive impairment (MCI), and culminate in dementia. While many studies have evaluated CSF tau and Abeta(42) as biomarkers of the dementia or prodromal stages of AD, we are unaware of any study to evaluate these potential CSF biomarkers of latent AD.


METHODS
We determined the ratio of CSF tau/Abeta(42) (T/Abeta) using Luminex reagents in 129 control individuals that spanned from 21 to 100 years of age; for comparison we included patients with MCI (n = 12), probable AD (n = 21), or other neurodegenerative diseases (n = 12).


RESULTS
We identified 16% of the control group with abnormally elevated CSF T/Abeta; all were 53 years or older. Using age-matched controls with normal CSF T/Abeta we showed that the high CSF T/Abeta subgroup of controls had significantly increased frequency of the epsilon4 allele of the apolipoprotein E gene and significantly increased risk of conversion to MCI during follow-up of up to 42 months suggesting that they had latent AD at the time of lumbar puncture.


CONCLUSIONS
These generally applicable methods establish cutoff values to identify control individuals at increased risk of conversion to mild cognitive impairment which may be useful to people weighing the risk-benefit ratio of new preventive therapeutics and to researchers striving to enrich clinical trial populations with people with latent Alzheimer disease.
Li
G
G
Mental Illness Research, Education, and Clinical Center and Department of Psychiatry, VA Puget Sound Health Care System, University of Washington, Seattle, WA, USA.
Sokal
I
I
Quinn
J F
JF
Leverenz
J B
JB
Brodey
M
M
Schellenberg
G D
GD
Kaye
J A
JA
Raskind
M A
MA
Zhang
J
J
Peskind
E R
ER
Montine
T J
TJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000523:psychology; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D012307:Risk Factors; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins