Linking Cognitive Impairment with Amyloid-ß Accumulation in Alzheimer's Disease: Insights from Behavioral Tests and FTIR Spectroscopy.

ABSTRACT

Background: Alzheimer's disease (AD) is a neurodegenerative disorder that progresses over time. Fourier Transform Infrared Spectroscopy (FTIR) analysis gives identification of the main metabolic changes that happen during neurodegeneration, by monitoring biochemical and molecular structure alterations that can help in AD diagnosis or treatment approach. Objective: The aim of the present work is to assess AD hallmarks in molecular structure of retina and monitor accumulation of amyloid beta42(Aß42) in brain and retina during disease progression. Methods: AD induced in rats by Aluminum Chloride (AlCl3). Retinal molecular structure during disease progression for 2,4,6 and 8 weeks was assessed by Fourier-transform infrared spectroscopy (FTIR) and the incidence of the disease was confirmed by a behavioural assessment; the Morris Water Maze test. Aß42 levels in the brain and retina were also measured. Results: The results indicated that cognitive impairment starting from 6 weeks of AlCl3 administration. Retinal concentration of Aß42 was significant increase (p < 0.05) from 2 weeks that precedes the observed increase of Aß42 in the brain which appeared after 4 weeks of AlCl3 administration. Multivariate principal component analysis discovers that the variance noticed in the infrared spectra due to AD condition and it is time dependent for progression of the disease. Conclusions: The accumulation of Aß42 is a sensitive early biomarker in retina for AD. FTIR analysis of the retina revealed changes in hydrogen bond formation or destruction, alterations in lipid chain length and branching accompanied by depleted lipid content and carbonization, as well as degeneration of the retinal tissue due to AD.