AIM To investigate whether the changes of amyloid ß1-42, total tau (t-tau), phospho-tau (p-tau), as well as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) expression and their concentration in the conjunctiva, tear, nasal mucosa and saliva of patients with Alzheimer's Disease (AD) may represent useful biomarkers to the diagnosis of AD and to identify subjects at risk of progression
DESIGN 2-year prospective, observational study
METHODS Patients fulfilling diagnostic criteria for typical AD (n= 40), prodromal AD (n=40), and non-AD cognitive impairment (n=40) and cognitively normal age and sex matched controls (n=40) will be included. All subjects will undergo extensive neuropsychological examination, and magnetic resonance imaging of the brain. Lumbar puncture and cerebro-spinal fluid (CSF) evaluation will be carried out in patients only. Enrolled patients have to show presence of medial temporal lobe atrophy and abnormal cerebrospinal fluid biomarkers with low amyloid ß1-42 concentrations, increased total tau concentrations or increased phospho-tau concentrations or combinations of the three. Patients and controls will be evaluated at baseline and every 6 months for 2 years. Biological samples of tears, conjunctival and nasal cytology as well as salivary samples will be collected at each time points. Levels of Amyloid Precursor Protein and its cleavage products, amyloid ß1-42, total and phosphorylated tau protein, NGF, pro-NGF, BDNF and pro-BDNF will be assessed by specific ELISA and Western blot and values will be compared among groups and over time using analysis of variance.
Tear and conjunctival ocular biomarkers levels, as well as nasal and salivary biomarkers concentrations will be further correlated to neuropsychological scores, structural data at MRI, and CSF values by linear or logistic regression analysis. Receiving operating characteristics curves will be calculated to identify the most useful diagnostic tool for AD
