RESUMO
BACKGROUND: An early and accurate diagnosis of Alzheimer's disease (AD) is important in order to initiate symptomatic treatment with currently approved drugs and will be of even greater importance with the advent of disease-modifying compounds. METHODS: Protein profiles of human cerebrospinal fluid samples from patients with AD (n = 85), frontotemporal dementia (n = 20), and healthy controls (n = 32) were analyzed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to verify previously discovered biomarkers. RESULTS: We verified 15 protein biomarkers that were able to differentiate between AD and controls, and 7 of these 15 markers also differentiated AD from FTD. CONCLUSION: A panel of cerebrospinal fluid protein markers was verified by a proteomics technology which may potentially improve the accuracy of the AD diagnosis.
Assuntos
Envelhecimento/fisiologia , Doença de Alzheimer , Demência/diagnóstico , Idoso , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/fisiopatologia , Biomarcadores , Cromogranina A/líquido cefalorraquidiano , Cistatina C , Cistatinas/líquido cefalorraquidiano , Diagnóstico Diferencial , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Ribonuclease Pancreático/líquido cefalorraquidianoRESUMO
Alzheimer's disease (AD) is the most common form of dementia found in all human populations worldwide, while vascular dementia (VaD) is the second most common form of dementia. New biomarkers for early and specific diagnosis of AD and VaD are needed to achieve greater insight into changes occurring in the brain and direct therapeutic strategies. The objective of this explorative study was to discover candidate protein biomarkers for the differential diagnosis between VaD and AD. Surface-enhanced laser desorption/ionization (SELDI) TOF-MS was used to differentially profile proteins and peptides in CSF samples from 28 AD patients and 21 patients with VaD. A combination of univariate (Kruskal-Wallis) and multivariate (independent component analysis) statistical approaches produced a list of 27 proteins and peptides that could differentiate between VaD and AD. These markers represent various physiological processes, such as protein degradation (ubiquitin), protease inhibition (cystatin C and alpha-1-antichymoptrypsin), and inflammation (C3a and C4a) that are known to be represented in neurodegenerative diseases.