Introduction:
The pathological process of Alzheimer's disease (AD) in the brain likely begins
20-30 years earlier than the emergence of its first clinical symptoms and symptoms of AD often overlap
with the symptoms of other primary causes of dementia. Therefore, it is crucially important to improve
early and differential diagnosis of the disease. Event-related potentials (ERP) measured non-invasively
by electroencephalography have shown diagnostic potential in AD.
Aims:
The aim of this study was to compare the efficiency of P300 and N200 potentials and reaction
time (RT) with commonly used protein biomarkers measured in the cerebrospinal fluid (CSF), including
amyloid β peptide (β1-42), total tau (t-tau), tau protein phosphorylated at threonine 181 (p-tau181), tau
protein phosphorylated at serine 199 (p-tau199), tau protein phosphorylated at threonine 231 (p-tau231),
and visinin-like protein 1 (VILIP-1) in differential diagnosis of AD in mild cognitive impairment (MCI)
and AD patients.
Subjects:
The study involved 49 AD patients, 28 patients with MCI, 4 healthy control subjects and 16
patients with other primary causes of dementia.
Results:
ERP (P300RT, N200RT, P300 counting and N200 counting) showed a moderate to strong correlation
with protein CSF biomarkers. We confirmed previous observations of moderate to strong correlation
between ERP and neuropsychological testing and showed that P300 latency and RT are shortened
in AD patients on therapy with acetylcholinesterase inhibitors. Using ERP and RT, a predictive model
for determination of AD likelihood in MCI patients was developed, detecting 56.3% of MCI patients
with high risk for development of AD in our cohort. MCI patients with pathological levels of Aβ1-42 had
prolonged P300 latency, indicating that a combination of ERP and CSF protein biomarkers could improve
the differential diagnosis of AD in MCI patients. Additionally, the results suggested the potential
of P300 latency in differentiating AD and FTD patients.
Conclusion:
Our data provide possible solutions for improvement of differential diagnosis of AD, and
reveal that the diagnostic efficiency of CSF protein biomarkers t-tau, p-tau181, p-tau199, p-tau231 and
VILIP-1 could be improved by adding ERP in clinical practice.
An immuno-enrichment free, validated quantification of tau protein in human CSF by LC-MS/MS
