Table 1.

Effects of the transmission of sample materials containing Aβ-, tau- or α-synuclein aggregates to rodents

References	Study design			Effect on protein aggregation in the CNS				Spread of observed aggregation effect	Neurodegeneration in the CNS	Non-transient clinical abnormalities	Severe or fatal disease
	Inoculum	Route	Recipients	Increase	Acceleration	Triggering	Causation
Aβ
Kane et al. [46]	Aβhu-AD	i.c.	Tg2576 mice		+			+	−1a	−1a	−1a
Meyer-Luehmann et al. [59]	Aβhu-AD	i.c.	APP23 mice		+			+	n.d.	n.d.	n.d.
	Aβmu	i.c.	APP23 mice		+			+	n.d.	n.d.	n.d.
	Aβmu	i.c.	APPPS1 mice		+			+	n.d.	n.d.	n.d.
Bolmont et al. [8]	Aβmu	i.c.	P301L mice2a		+			+	n.d.	n.d.	n.d.
Eisele et al. [26]	Aβmu	i.c.	APP23 mice3		+			+	n.d.	n.d.	n.d.
Eisele et al. [27]	Aβmu	i.p.	APP23 mice		+			+	n.d.	n.d.	n.d.
Rosen et al. [78]	Aβhu-AD	i.c.	APP21 rats			+		–	n.d.	n.d.	n.d.
Morales et al. [61]	Aβhu-AD	i.c.	HuAPPwt mice			+		+	n.d.	n.d.	n.d.
Stöhr et al. [88]	Aβmu	i.c.	APP23:Gfap-luc mice	+				+	n.d.	n.d.	n.d.
	Aβpreformed	i.c.	APP23:Gfap-luc mice	+				+	n.d.	n.d.	n.d.
Duran-Aniotz et al. [25]	Aβhu-non AD	i.c.	APPswe/PSENΔE9 mice	+				+	n.d.	n.d.	n.d.
Heilbronner et al. [37]	Aβmu	i.c.	APP23 mice		+			+	n.d.	n.d.	n.d.
	Aβmu	i.c.	APPPS1 mice		+			+	n.d.	n.d.	n.d.
Tau
Clavaguera et al. [17]	taumu	i.c.	ALZ17 mice			+		+	−1b	n.d.	n.d.
Clavaguera et al. [18]	tauhu	i.c.	ALZ17 mice			+		+	−1c	n.d.	n.d.
	tauhu	i.c.	C57BL/6 wt mice				+	+	n.d.	n.d.	n.d.
	taumu	i.c.	ALZ17 mice			+		+	n.d.	n.d.	n.d.
Lasagna-Reeves et al. [51]	tauhu	i.c.	C57BL/6 wt mice				+	+	n.d.	−1d	−1d
Iba et al. [40]	taupreformed	i.c.	P301S PS19 mice		+			+	−1e	n.d.	−1f
Clavaguera et al. [19]	taumu	i.p.	P301S mice	+				+	n.d.	n.d.	n.d.
Sanders et al. [80]	taumu	i.c.	P301S PS19 mice		+			n. d.	n.d.	n.d.	n.d.
	taupreformed	i.c.	P301S PS19 mice		+			n. d.	n.d.	n.d.	n.d.
	tauHEK cells	i.c.	P301S PS19 mice		+			+4	n.d.	n.d.	n.d.
α-Synuclein
Mougenot et al. [62]	α-synmu	i.c.	TgM83+/+ mice		+			+	n.d.		+(Acceleration)
Luk et al. [55]	α-synpreformed/mu	i.c.	C57BL/6 wt mice				+	+	+(Causation)	+(Causation)	–1j
Luk et al. [56]	α-synmu	i.c.	TgM83+/+ mice		+			+	+(Acceleration)		+(Acceleration)
	α-synpreformed/hu	i.c.	TgM83+/+ mice		+			+	+(Acceleration)		+(Acceleration)
Masuda-Suzukake et al. [58]	α-synhu-DLB	i.c.	C57BL/6 wt mice				+	+	n.d.	n.d.	n.d.
	α-synpreformed/mu	i.c.	C57BL/6 wt mice				+	+	−1g	−1h	−1h
	α-synpreformed/hu	i.c.	C57BL/6 wt mice				+	+	−1g	−1h	−1h
Watts et al. [92]	α-synhu-MSA	i.c.	TgM83+/− mice		+			+	n.d.		+(Acceleration)
Guo et al. [33]	α-synpreformed/hu	i.c.	P301S P19 mice2b		+			+	n.d.	n.d.	n.d.
Recasens et al. [75]	α-synhu-PD	i.c.	C57BL/6 wt mice				+	+	+(Causation)	+(Causation)	−1i

Aβ-, tau- or α-syn inocula containing Aβ-, tau- or α-synuclein aggregates, respectively (subscripted indices indicate the following origins: HEK cells HEK cell lines that stably expressed the aggregation-competent repeat domain of tau, hu-AD humans with AD, hu-DLB humans with DLB, hu-non AD humans without AD, hu-MSA humans with MSA, hu-PD humans with PD, mu mice, preformed in vitro preformed peptide or protein aggregates, preformed/hu or preformed/mu in vitro preformed aggregates of human or murine proteins, respectively), n.d. not determined, + positive finding reported, − negative finding reported, i.c. intracerebral administration to recipients, i.p. intraperitoneal administration to recipients

^1a−i Negative up to 5^a, 15^b,c,g, 11^d, 6^e,h,j, 9^f or 17ⁱ months post-inoculation (g—negative finding refers to absence of dopaminergic degeneration)

^2a,b Indication of cross-seeding by Aβ_mu and α-syn_preformed/hu of mutated human tau, respectively

³ Intracerebral inoculation with Aβ_mu was performed by injection of liquid sample materials or implantation of steel wires

⁴ Positive finding with one of the tested HEK cell clones