Table 1 Summary of selected Aβ seeding studies
Reference | Source of seed (route of injection) | Host Line | Host Onset | Host Pathological Features | Age Observed (Age at Time of Injection) | Pathological Features of seed | Pathological Features of Induced Aβ Pathology |
|---|---|---|---|---|---|---|---|
[4] | Human (IHC) | Tg2576 | ~ 9 months | Mixed core > diffuse | 8 months (3 months) | “plaques and Neurofibrillary tangles” | Primarily diffuse deposits, largely Aβ42 |
[5] | Human (IHC) | Tg2576 | ~ 9 months | Mixed core > diffuse | 8 and 15 months (3 months) | “plaques and Neurofibrillary tangles” | Primarily diffuse in cortex with some cored deposits in corpus callosum |
[6] | Human (IHC) | APP23 | 6–9 months | Mixed core > diffuse | 9 months (5 months) | “plaques and neurofibrillary tangles” | Significant Aβ deposition that appeared diffuse |
Mouse (APP23) (IHC) | 7–9 months (5 months) | Fibrillar, congophilic, Aβ40 > Aβ42 | “Diffuse and filamentous”. Some congophilic parenchymal deposits near vessels. Dystrophic neurites. | ||||
Mouse (APPPS1) (IHC) | 8 months (5 months) | Fibrillar, congophilic, Aβ42 > Aβ40 | “course, punctate” | ||||
Synthetic Aβ and WT brain extract | Limited deposition, similar to below | ||||||
Synthetic Aβ42 (100-1000X) (IHC) | 9 months (5 months) | Fibrillar, congophilic | Some deposits in dentate gyrus, amorphous mass (largely injectate) | ||||
Mouse (APP23) (IHC) | APPPS1 | 3–6 months | Mixed core > > diffuse | 3 and 5 months (2 months) | Fibrillar, congophilic, Aβ40 > Aβ42 | “mixture of filamentous and compact” | |
Mouse (APPPS1) (IHC) | Aβ42 > Aβ40 | “course and punctate deposition” | |||||
[7] | Mouse (APP23) (Varied: Olf Bulb, parietal cortex, entorhinal cortex, striatum, IHC) | APP23 | 6–9 months | Mixed core > diffuse | 3 months post injection (2–5 months, proximal to injection site), more robust 6 months after injection. | Fibrillar, congophilic, Aβ40 > Aβ42 | Parenchymal diffuse Aβ with variable congophilic core plaques and vascular deposits (see Table S1 for more details). |
[8] | Mouse (APP23) IP injection | APP23 | 6–9 months | Mixed core > diffuse | 8–9 months (2 months) | Fibrillar, congophilic, Aβ40 > Aβ42 | CAA carrying into nearby parenchyma. Congophilic vascular Aβ, surrounded by “diffuse, Congo red-negative Aβ deposits”. |
[9] | Mouse (APP23) (IHC) | Tg (APP23:Gfap-luc) | 6–9 months | Mixed core > diffuse | 12 months (~ 2 months) | Fibrillar, congophilic, Aβ40 > Aβ42 | “large numbers of small Aβ plaques … [and] more diffuse Aβ deposits”. |
[10] | Human (IHC) | human WT APP Hetero zygotes (HuAPPwt) | N/A | N/A | 450 days, 615 days, 750 days (165 days) | “plaques and Neurofibrillary tangles” | Diffuse deposits (450 and 615 days). 3/7 mice ThioS positive (750 days). |
[11] | Mouse (APP23, fractionated proteinase K treated) (IHC) | APP23 | 6–9 months | Mixed core > diffuse | 7–9 months (3–4 months) | Fibrillar, congophilic, Aβ40 > Aβ42 | Mixture diffuse and congophilic deposits. Aβ deposits small and punctate, some congophilic. |
Mouse (APP23, M or F, extra-sonicated) (IHC) | |||||||
[12] | Mouse (APP23) (IHC) | R1.40 APP (homozygous) | ~ 15 months | Mixed core > diffuse | 9 months (3 months) | Fibrillar, congophilic, Aβ40 > Aβ42 | Largely diffuse deposits in parenchyma and near vessels. |
15 months (9 months) | |||||||
15 months (3 months) | |||||||
[13] | Mouse (APP23, CRND8) (ICV) | APP23:Gfap-luc | 6–9 months | Mixed core > diffuse | 330–385 days post injection (2 months) | Fibrillar, congophilic | Increased Aβ deposition; morphology not described. |
Brain purified fibrils (ICV) | Fibrils. 15-20x more Aβ-rich than non-purified | Increased Aβ deposition; morphology resembles cored plaques. | |||||
Synthetic WT Aβ40 (ICV) Synthetic S26C Aβ40 (ICV) | Fibrillar, congophilic | Increased Aβ; morphology resembles cored plaques in corpus callosum. | |||||
Mouse (APP23) (IHC) | APP23 | 6–9 months | Mixed core > diffuse | 7–9 months (4–6 months) | Fibrillar, congophilic, Aβ40 > Aβ42 | Diffuse deposits in molecular layer of dentate gyrus that exhibit spectral properties of seed source when stained with trimeric polythiophene acetic acid | |
Mouse (APPPS1) (IHC) | Fibrillar, congophilic, Aβ42 > Aβ40 | ||||||
Mouse (APP23) (IHC) | APPPS1 mice | 3–6 months | Mixed core > > diffuse | 3–4 months (1.5–2 months) and 6 months (3 months) | Fibrillar, congophilic, Aβ40 > Aβ42 | ||
Mouse (APPPS1) (IHC) | Fibrillar, congophilic, Aβ42 > Aβ40 | ||||||
[16] | Synthetic Aβ40 (NaP) (ICV) | APP23:Gfap-luc | 6–9 months | Mixed core > diffuse | 330 days after injection (6–8 weeks) | (long straight fibrils, rarely short fibrils) | Mixed ThioS-positive compact deposits with dense Thio-S negative deposits. |
Synthetic Aβ42 (NaP) (ICV) | (long fibrils, mostly short fibrils) | ||||||
Synthetic Aβ40 (NaP/SDS) | (long straight fibrils) | ||||||
Synthetic Aβ42 (NaP/SDS) | (long fibrils with some twists) | ||||||
[17] | Mouse (APP23/APPPS1) (IP injection) | APP23 | 6–9 months | Mixed core > diffuse | 7–8 months (1–2 months), more robust 7–8 months after injection | Fibrillar, congophilic, | Diffuse parenchymal, variable vascular deposition. 5–15% deposits congophilic. |
Mouse (APP23/APPPS1) (IP injection) | homozygous R1.40 | 10–14 months | Mixed core > diffuse | Somewhat at 9–10 months (1–2 months), more robust 10–12 months after injection. | Fibrillar, congophilic, | Deposits of neocortex in younger groups largely vascular, but in older groups more parenchymal diffuse plaques. | |
Mouse (APP23/APPPS1) (IP injection) | hemizygous APP23 with murine APP −/− | 9–10 months | 9–10 months (1–2 months) | Fibrillar, congophilic, | Diffuse parenchymal, vascular deposits evidence with 5% congophilic. | ||
[18] | Human (fixed) (IHC) | APP23 | 6–9 months | Mixed core > diffuse | 7–8 months (3–4 months) | “plaques and neurofibrillary tangles” | Small, compact, punctate Aβ deposits. Thioflavin-S and Congo Red staining not reported. |
Mouse (APPPS1, fresh frozen) (IHC) | Fibrillar, congophilic, | ||||||
Mouse (APPPS1, fixed and cryoprotected) (IHC) | |||||||
Mouse (APP23, fresh frozen) (IHC) | |||||||
Mouse (APP23, fixed and cryoprotected) (IHC) | |||||||
[19] | Human (fresh frozen supernatant from formic acid-soluble fraction) (IHC) | APP23 | 6–9 months | Mixed core > diffuse | 12 months (4 months) | “plaques and Neurofibrillary tangles” | Diffuse Aβ depositions. |
Human (supernatant mixed with CSF) (IHC) | 10–11 months (3–4 months) | “plaques and Neurofibrillary tangles” | Robust Aβ deposition, largely diffuse. | ||||
[20] | Mouse (APP23 mouse hippocampi seeded 1 and 30 days prior with APP23 brain tissue) | APP23 mice (male) | 7 and 11 months (3 months) | Some congophilic deposits, both parenchymal and vascular. | |||
[21] | Mouse (APP23) (IHC) | APP23 mice | 6–9 months | Mixed core > diffuse | Robust at 9–10 months (3–4 months) | Fibrillar, congophilic, Aβ40 > Aβ42 | “Diffuse and filamentous” Aβ deposition. |
Mouse (APPPS1) (IHC) | Robust at 9–10 months (3–4 months) | Fibrillar, congophilic, Aβ42 > Aβ40 | “Punctate and compact” Aβ deposition | ||||
[22] | Mouse (5xFAD) (IHC) | 5xFAD | ~ 4 months (hippocampus) | Mixed core > > diffuse | 13 weeks initial plaques observed; also 4 months (7 weeks) | Fibrillar, congophilic, Aβ42 > Aβ40 | Punctate and compact deposits in hippocampus and dentate gyrus |
Mouse (APP23) (IHC) | APP23 | 6–9 months | 9 months (6 months) | Fibrillar, congophilic, Aβ40 > Aβ42 |