## 1 Introduction  
Alzheimer's disease (AD) is the most frequent type of dementia [1], which includes a variety of diseases such as AD, vascular dementia, dementia with Lewy bodies, Parkinson's disease, and more. Dementia is caused by the death or malfunction of nerve cells in the brain, which results in a decline in memory and in several cognitive abilities. In AD, the pathological abnormalities are characterized by a gradual loss of axons and neurons, together with the presence of neurofibrillary tangles and amyloid plaques in the brain. According to the new criteria for diagnosing AD [1], the disease includes three stages: preclinical AD, Mild Cognitive Impairment (MCI) due to AD, and dementia due to AD. During the preclinical AD stage, which may last up to 20 years, no cognitive decline and memory loss symptoms occur. However, the pathogenic process in this stage already induces measurable changes in the brain, in the cerebrospinal fluid (CSF), and in the blood. Therefore, diagnostic tools for early detection of the disease, based on these pathological expressions, may have a significant advantage. Currently, there is no treatment available for preventing, or curing AD, but there are enormous efforts, worldwide, towards developing treatment. In order for treatment to be effective, there is a crucial need for early detection of AD. One of the promising methods for early detection of AD uses measurements of cerebrospinal fluid (CSF) amyloid-beta and tau protein concentrations. Due to the accumulation of amyloid-beta in the brain, there is a significant reduction in CSF A\(\beta\)42 levels. On the other hand, the release of tau and phosphorylated-tau during the neurodegeneration and the neurofibrillary tangles creation, increases the levels of these proteins in the CSF [2]. As a result, the CSF concentration of the A\(\beta\)42, total tau, and p-tau is highly correlated with early diagnosis of AD. Several groups have shown the possibility of predicting the development of MCI to AD, years before the clinical diagnosis of the disease, based on these biomarkers [2; 3; 4; 5; 6]. [PERSON] et al. [3] showed that a combination of CSF T-tau and A\(\beta\)42/P-tau ratio yielded high sensitivity and specificity for detection of incipient AD in patients with MCI who were followed for a period of 4-6 years. The optimum cutoff value was A\(\beta\)42:P-tau \(<\) 6.5 for the incipient AD patients at baseline. The follow-up of this study was extended [4] for up to 11.8 years (median = 9.2 years). Using a cutoff value of 6.16 for the A\(\beta\)42:P-tau ratio, they predicted the future development of AD dementia with a sensitivity of 88% and a specificity of 90%. A multi-center research [6] covering 12 centers in Europe and in the USA and including more than 1500 individuals (with AD, MCI and healthy controls) followed MCI patients for at least two years. A comprehensive statistical analysis was performed in order to determine the possibility to predict incipient AD in MCI patients based on their A\(\beta\)42, total tau and P-tau CSF levels. Their results indicated that the combination of A\(\beta\)42:P-tau ratio and total tau identified incipient AD with a sensitivity of 83% and specificity of 72%. These results are highly significant but are less accurate than the previously reported results. Possible reasons are large variability between the centers, lack of standardization, and relatively short follow-up. In order to measure the A\(\beta\)42, total tau, and P-tau CSF concentrations, a lumbar puncture process was performed and CSF samples were collected. The lumbar puncture procedure has many risks, side effects, and complications [7], which limit its potential to be an annual test for early AD diagnosis. This limitation may be resolved by less invasive methods that enable measurements of the CSF protein concentrations using optical techniques. Many optical techniques were developed for quantifying tissue components, proteins and drugs. Most of the methods are based on transmission or diffused reflection spectroscopy.