Dataset Information

CSF biomarker changes precede symptom onset of mild cognitive impairment.

ABSTRACT:

Objective

This study evaluated longitudinal CSF biomarker measures collected when participants were cognitively normal to determine the magnitude and time course of biomarker changes before the onset of clinical symptoms in subjects with mild cognitive impairment (MCI).

Methods

Longitudinal CSF collection and cognitive assessments were performed on a cohort of 265 participants who were cognitively normal at their baseline assessment and subsequently developed MCI or dementia. CSF ?-amyloid 1-42 (A?1-42), total tau (t-tau), and phosphorylated tau (p-tau) were determined longitudinally. Consensus diagnoses were completed annually. Cox regression analyses were performed, with baseline CSF values and time-dependent rate of change in CSF values as covariates (adjusted by baseline age, race, and education), in relation to time to onset of mild cognitive symptoms.

Results

The mean time from baseline to onset of mild cognitive symptoms was 5.41 years. Increased risk of progressing from normal cognition to onset of clinical symptoms was associated with baseline values of A?1-42, p-tau, and the ratios of p-tau/A?1-42 and t-tau/A?1-42 (p < 0.002). Additionally, the rate of change in the ratios of t-tau/A?1-42 (p < 0.004) and p-tau/A?1-42 (p < 0.02) was greater among participants who were subsequently diagnosed with MCI.

Conclusions

Baseline differences in CSF values were predictive of clinical symptoms that were a harbinger of a diagnosis of MCI more than 5 years before symptom onset, and continue to show longitudinal changes as cognitive symptoms develop, demonstrating that baseline and longitudinal changes in CSF biomarkers are evident during the preclinical phase of Alzheimer disease.

SUBMITTER: Moghekar A

PROVIDER: S-EPMC3821715 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Publications

CSF biomarker changes precede symptom onset of mild cognitive impairment.

Moghekar Abhay A Li Shanshan S Lu Yi Y Li Ming M Wang Mei-Cheng MC Albert Marilyn M O'Brien Richard R

Neurology 20131016 20

<h4>Objective</h4>This study evaluated longitudinal CSF biomarker measures collected when participants were cognitively normal to determine the magnitude and time course of biomarker changes before the onset of clinical symptoms in subjects with mild cognitive impairment (MCI).<h4>Methods</h4>Longitudinal CSF collection and cognitive assessments were performed on a cohort of 265 participants who were cognitively normal at their baseline assessment and subsequently developed MCI or dementia. CSF ...[more]

PMID: 24132375

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Project description:Research shows that late mild cognitive impairment (LMCI) has a high risk of turning into Alzheimer's disease (AD). Due to the invasion of detection methods and physical damage to the patients, it is not a convenient way to diagnose and detect early AD and LMCI by cerebrospinal fluid (CSF) data. So there is an urgent need to find the correlation between peripheral biological data and CSF data in the brain, and to find new diagnostic methods through changes in the peripheral biological data. Studies have shown that during the pathogenesis of LMCI and AD, peripheral immune cells specifically infiltrate into the brain through the blood-brain barrier, causing an imbalance in the brain's immune response and dysregulating the clearance of Aβ in CSF. Therefore, in this paper, canonical correlation analysis (CCA) algorithm is presented to derive the correlation between peripheral and CSF biomarkers based on LMCI peripheral gene expression data and plasma marker information. Firstly, to explore the influence of the infiltration of peripheral blood immune cells on the brain, the abundance of 28 immune cells were calculated by using the gene set enrichment analysis algorithm of LMCI samples. Then, to identify the correlation between biomarkers inside and outside of the brain, we performed CCA to calculate the relationship between CSF and peripheral biomarkers. Results of CCA showed significant correlations between the variable sets of 8 peripheral biomarkers and the variable sets of CSF biomarkers (at 0.794). Finally, according to Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis, it was found that the obtained peripheral biomarkers are involved in many immune-related pathways and functions which can be activated in peripheral blood of LMCI patients. Most related genes enriched in immune-related pathways and functions were up-regulated. Through receiver operating characteristic curve (ROC) analysis, it was also found that FP40/FP42 and type 1 T helper can accurately predict the pathological changes of LMCI (at 0.747).

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Dataset Information

CSF biomarker changes precede symptom onset of mild cognitive impairment.

Objective

Methods

Results

Conclusions

Publications

CSF biomarker changes precede symptom onset of mild cognitive impairment.

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