Fig 2: SCRN1 in HCHWA-D. SCRN1/Aß immunostaining showed no accumulation of SCRN1 in either vascular (a, b) or parenchymal lesions (c, d)

Fig 3: SCRN1 only colocalizes with AD-associated pathology in a CBD case with AD comorbidity. a-c Astrocytic plaques (asterix) consistent with CBD pathology contained PHF1 positive pTau, but not SCRN1 (a). RD4 (b) and RD3 (c) immunostaining confirmed 4R tau specificity. d-f RD4 positive pre-tangles (e) associated with CBD pathology showed immunoreactivity for PHF1 (d) but not SCRN1. g-i Presence of SCRN1 in lesions containing PHF1(g), RD4 (h) and RD3(i) positive pTau consistent with AD-associated NFTs pathology and dystrophic neurites (arrows). Scale bar for inserts: 25 µm

Fig 4: SCRN1 had limited immunoreactivity in ARTAG-associated thorn-shaped astrocytes in a mixed pathology case. a, b SCRN1 showed prominent accumulation in AD-associated NFTs. c, d Absence of SCRN1 in PSP-associated tufted astrocyte. e, f Minimal accumulation of SCRN1 around the nucleus in a thorn-shaped astrocyte

Fig 5: Secernin-1 accumulates in pTau aggregates in AD, DS and PART but not in PiD, CBD and PSP. a SCRN1 colocalization with PHF1 in AD, DS and AD, PART, Pick’s disease, CBD and PSP. Representative images show SCRN1 staining in the hippocampus in AD, DS and AD, PART and Pick’s disease and of SCRN1 staining in the basal ganglia in CBD and PSP. SCRN1 (green) accumulated in neurofibrillary tangles and in dystrophic neurites in AD, Down syndrome and PART but not in PHF1 positive aggregates (red) in PiD, CBD or PSP. b-e SCRN1 levels were significantly higher in PHF1 positive NFTs and dystrophic neurites than in surrounding neurons in both DS (b) and PART (c), similar to AD. There was limited/no co-localization of SCRN1 with pTau positive neuropathological lesions in Pick’s disease (d), Corticobasal Degeneration and Progressive Supranuclear Palsy (e). *** p-value < 0.001, ** p-value < 0.01, * p-value < 0.05; two-tailed paired t-test