Can CSF study predict AD in those with Mild Cognitive Impairment? Current Opi Psy.May.2013

06.06.2013

Interest in biomarkers in psychiatric disorders is increasing . These might help in predicting the disorder/identifying disease process early on/ evaluating treatment effects etc. CSF biomarkers in Alzheimer’s disease (AD)  is a good example for this.

Christoffer Rose ́ and Henrik Zetterberg review the state of our knowledge about CSF biomarkers  in AD in this article.

Pathology: Tau is a normal protein present in the axons of neurons. It promote axonal stability through the binding to micro- tubules. This ability is disrupted in its phosphorylated state, which leads to tau aggregation, impaired axonal transport and, eventually, neuronal degeneration.Phosphorylated Tau is the major constituent of neurofibrillary tangles.

Senile plaques contain extracellular amyloid protein most abundant of which is  the 42 amino-acid long variant (Ab42).It is thought that gradual accumulation of Ab in the brain serves as the initiating event in the disease process.

Markers in AD

Total Tau: CSF concentration of total tau (T-tau) is increased around 300% in AD as compared with control levels.High levels seen also in acute stroke, head trauma and  Creutzfeldt – Jakob disease .

P-Tau: P-tau in the CSF is increased in AD. This is a surrogate marker for tangle pathology and is more specific for AD  and may therefore be useful in the differential diagnosis against other dementias. 

Ab42: A reduction in the concentration of CSF Ab42 to about 50% of controls can be seen in AD.(due to sequestration of Ab42 into senile plaques).

High CSF concentrations of T-tau and P-tau together with low Ab42 differentiate patients with AD as well as MCI ( Mild cognitive impairment) due to AD from controls with sensitivity and specificity around 75–95%.

Others markers of interest: Markers for enzymes that are involved in production of amyloid protein, concentration of B amyloid oligomers,Inflammatory biomarkers (particularly CSF TGF-b which is consistently  increased),markers for microglial &  astrocytic activation, markers for synaptic loss .

The results of the

plasma biomarkers are currently inconsistent. 

Conclusion: 

CSF biomarkers provide high diagnostic accuracy in the discrimination of patients with AD.Biomarkers are highly predictive of AD with dementia in patients with mild cognitive impairment (due to AD), and have been included in new diagnostic criteria.

Summary of the article:    

Cerebrospinal fluid biomarkers for pathological processes in Alzheimer’s disease.

Rosén C, Zetterberg H.Curr Opin Psychiatry. 2013 May;26(3):276-82

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