Background: Protein misfolding and beta amyloid (Aβ) aggregation can induce Alzheimer’s disease (AD)-like by Aluminium (Al) in rat hippocampal brain tissue. Al can produce free radicals, trigger membrane peroxidation and protein oxidation disrupt acetylcholine content leading to synaptic loss, neural death and cognitive dysfunction symptoms that are strongly associated with AD pathogenesis. Medicinal plant  Lepedium sativum (LS) water extract proved promising curative effects and its ability to restore the protein integrity, with a marked clearing of Aβ that was reported in our previous reports.
Methods: In this study we utilized Synchrotron Fourier Transform Infrared Microspectroscopy (SFTIRM) and multivariate analysis to investigate and monitor more thoroughly the process of protein misfolding in response to Al and curative effect of LS treatment as well. Results: The results revealed a marked increase in the protein β-structure in AD group after 42d of AL intoxication over the random coil structure. Thus, suggesting two transit phases of Aβ formation.  Meanwhile, at late stage of Al neurotoxicity after 65d ~91\% of the amide I is random coil and the rest is anti-parallel β-sheets, alpha helix structure is absent in both tested times too. Incredibly, this random coil structure is totally absent in the curative group; instead, it is dominated by a drastic increase in the protein βstructure suggesting the clearance of Aβ takes place through β-structure transit phase. The role of β –structure & random coil as a transit phase in transformation of Aβ and/or clearance in response to AL and LS treatment after at 42d & 65d respectively is supported by different calculated \% area ratio measurements as well.  
Conclusions: LS treatment strongly proved its reversed action on Aβ misfolding that helped to restore the hippocampal protein integrities. SFTIRM gave unique and deeper cluster of data over the conventional FTIR in studying hippocampal brain tissue.