File Name : fig.s1.pdf Caption : fig. s1. high-spatial resolution hyperspectral images of 6 and 12-months old ad mice. the images were generated by selecting filters for each frequency value in project five 5.0 witec software. main frequencies were able to identify in situ the core of the amyloid plaque: phe (1007/10 cm-1) amide iii β sheet (centered at 1233/60 cm-1), amide i β sheet (1670/10 cm-1). ch2 stretching of the total lipid (2850/10 cm-1) forming the lipid halo, ch2 stretching of the total lipid and protein (2880/10 cm-1) and ch3 stretching of the total lipid and protein (2930/10 cm-1). nuclei cells at dna frequency (791/25 cm-1). note amide i and iii α helix shows lipid halo structures as well, this is probably due to the overlapping frequencies of protein and lipid in these range (see frequencies table). ch2 and ch3 (2880/10 cm-1 and 2930/10 cm-1 respectively) frequencies related to protein and lipid stretching forms the lipid halo by also shown the amyloid plaque. in ch3 frequency value, the contrast of the plaque is greater compared to ch2 (2880 cm-1). scale bar, a-b, 10 µm; c-d, 20 µm; e-f, 10 µm. lip: lipid; prot: protein. File Name : fig.s2.tif Caption : fig. s2. accumulated variance for each principal component. File Name : fig.s3.tif Caption : fig. s3. variation of the total within-cluster mean square for each number of clusters. File Name : fig.s4.tif Caption : fig. s4. screen plot showing the relevance of each pc to the data variance. File Name : fig.s5.tif Caption : fig. s5. pc loadings for each of the nine pcs used for the cluster analysis. File Name : fig.s6.tif Caption : fig. s6. cluster maps of ad mice brain. on left column, hyperspectral raman images (a-d), showing dense-core amyloid plaques (red), lipid (yellow) and dna (blue). on right, cluster maps (a’-d’). amyloid plaque is well defined in both young and aged mice by clusters 5 and 7. however, clusters 6 and 8 distribution is more pronounced in lipid halo of the tg12 than tg6. scale bar 10 µm.