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Table 1 Summary of selected Aβ seeding studies

From: Remodeling Alzheimer-amyloidosis models by seeding

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.
[6, 14, 15] 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
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