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Dement Geriatr Cogn Disord. 2012;33(1):1-5. doi: 10.1159/000335729. Epub 2012 Feb 13.

Cerebrospinal fluid biomarkers and proximity to diagnosis in preclinical familial Alzheimer's disease.

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  • 1Mary S. Easton Center for Alzheimer's Disease Research at UCLA, Los Angeles, Calif., USA.

Abstract

BACKGROUND/AIMS:

Biological markers of utility in tracking Alzheimer's disease (AD) during the presymptomatic prodromal phase are important for prevention studies. Changes in cerebrospinal fluid (CSF) levels of 42-amino-acid β-amyloid (Aβ(42)), total tau protein (t-tau) and phosphorylated tau at residue 181 (p-tau(181)) during this state are incompletely characterized.

METHODS:

We measured CSF markers in 13 carriers of familial AD (FAD) mutations that are fully penetrant for causing AD (PSEN1 and APP) and in 5 non-mutation-carrying family members.

RESULTS:

Even among the entirely presymptomatic mutation carriers (n = 9), Aβ(42) was diminished (388.7 vs. 618.4 pg/ml, p = 0.004), and t-tau (138.5 vs. 50.5 pg/ml, p = 0.002) and p-tau(181) (71.7 vs. 24.6 pg/ml, p = 0.003) were elevated. There was a negative correlation between Aβ(42) levels and age relative to the family-specific age of dementia diagnosis.

CONCLUSIONS:

Our data are consistent with a decline in CSF Aβ(42) levels occurring at least 20 years prior to clinical dementia in FAD.

Copyright © 2012 S. Karger AG, Basel.

PMID:
22343824
[PubMed - indexed for MEDLINE]
PMCID:
PMC3696356
Free PMC Article

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