neup12765-sup-0001-FileS1.jpgJPEG image, 3.3 MB

Appendix S1 Histological observations of the brain stem and basal ganglia from cases 2, 3, and 4. In the medial portion of the substantia nigra (SN), NFTs and NTs are seen in all cases (A-C), most prominently in case 2 with very early-onset AD (A). In the locus coeruleus (Lc), where tau deposition is known to occur first, NFTs and NTs are uniformly seen in all cases (D-F). In the putamen (Put), amyloid deposits are also most abundant in case 2 (G). Tau deposits are observed in the large neuron, with many NTs in the ventral putamen (J-L), where astrogliosis is evident (M, N). AT-8 (A-F, J-L), Aβ11-28 (G-I), glial fibrillary acidic protein (GFAP) (M, N) staining. Scale bars: 100 μm (A-N).

neup12765-sup-0002-FileS2.jpgJPEG image, 2.1 MB

Appendix S2 Histological observations of the superior frontal (A-D, I-L) and occipital primary visual cortices (E-H, M-O) from cases 3 and 4. In case 3, amyloid deposits are abundant in the superior frontal cortex (B) and are less abundant in the occipital cortex, where amyloid angiopathy is observed (E, F). There are moderate numbers of NFTs and NTs in the superior frontal cortex (C, Q). However, NFTs and NTs are sparse in the occipital cortex (G). Astrogliosis is prominent in the gray-white matter junctions (D, H, R). In case 4, amyloid angiopathy is prominent in the superior frontal cortex (I, J) and occipital cortex (M, N). In contrast, NFTs and NTs are sparse in the superior frontal (K, S) and occipital cortices (O). Astrogliosis is observed in the peri-vascular areas (L, P, T). HE (A, E, I, M), Aβ11-28 (B, F, J, N), modified Gallyas-Braak (C, G, K, O, Q, S), GFAP (D, H, L, P, R, T) staining. Scale bars: 200 μm (A-P), 50 μm (Q-T). Q-T corresponds to the box areas in the upper column.

neup12765-sup-0003-FileS3.jpgJPEG image, 2.4 MB

Appendix S3 Histological observations of the hippocampal CA1 and subiculum in cases 1–4. NFTs and NTs are most abundant in case 2, with very early onset. Cases 3 and 4 are equally affected. Although memory disturbance in cases 1, 3, and 4 was relatively mild, they also have numerous NFTs and NTs in the hippocampus, especially in the subiculum. Case 2 has extremely abundant NFTs and NTs. In case 3, NFTs and NTs are obviously less abundant in the right side than in the left side. Modified Gallyas-Braak staining (A-J). Scale bars: 200 μm (A-J).