Table 1.

Transgenic murine models of Alzheimer’s disease phenotype and neuropathological aspects of four transgenic murine models of Alzheimer’s disease derived from the original ‘source’ references and unpublished data [12,14–20]

Tg-AD model	Straina	Age of SP onsetc	Tg-AD promoter/transgened	SPDe	CNSf	Synaptic pathologyg	Retinal pathologyh	Source reference
Tg2576	C57B6J X SJL F1 hybridb	10	Hamster prion promoter/human APP695 cDNA with K670N/M671L	+ + + +	+ +	+ + +	+ +	[2,8,12,15]
PSAPP	C57BL6/D2AFa	6	Tg2576×PSEN1M146L	+ +	+	–	+	[2,16–18]
3xTg-AD	Hybrid 129/ C57BL6a	6	Thy1 promoter/APP695-Swedish/Tau isoform 4R0N(P301L mutation)/PSEN1M146L	+ +	++ + +	+	+	[2,12,19]
5xFAD	C57BL6/SJLb	2	Thy1 promoter/B6SJL-Tg(APPSwFlLon,PSEN1M146L*L286V)6799Vas/J	+ + + +	+ + + +	+ + + +	+ + + +	[2,12,20]

These studies are the first to comparatively analyze Aβ peptide levels in the retina in four different transgenic murine models of Alzheimer’s disease (Tg-AD) models; Aβ peptide levels in the brain are comparable with several previous studies [15–22]. Symptomatic Tg-AD models exhibit variable senile plaque density [SPD; as seen anywhere within the central nervous system (CNS) in aged Tg-AD mice], and synaptic neuropathology (as determined by microscopic and molecular abundance measures; see below; unpublished observations); +detected, + + moderate abundance, + + + high abundance; + + + + extensive phenotype; see also references [2,12,14–20]. The scoring system adapted from [2,12], also took into consideration additional Tg-AD characteristics listed at the Tg-AD website http://www.alzforum.org/res/com/tra/app/default.asp, in addition to observed deficits in the abundance of several key cytoarchitectural and synaptic support proteins, including neurofilament light chain, spectrin, synaptophysin, synapsin-2, and syntenin (data not shown) [2,12], and from observations made in the original source reference for each Tg-AD type (rightmost column).

Table revised and modified from references [2,8,12,15–20].

^aGenetic background strain.

^bTg2576 and 5xFAD mice are generated from C57B6JxSJLF1 and C57Bl6/SJL hybrids, but only age-matched C57BL6/SJL and C57BL6 control mice were analyzed for Aβ40 and Aβ42 peptide abundance in these studies (see Table 2; http://www.alzforum.org/res/com/tra/app/TGCRND8.asp http://www.alzforum.org/res/com/tra/app/).

^cOnset (in months) of first appearance of senile plaques (SP) [2,8,12,15–20].

^dIndividual Tg-AD promoter constructs are described in more detail in source references (right-most column).

^eSPD (highest SPD per mm² observed) and determined as previously described [21].

^fCNS-specific expression of amyloid [2,15–20].

^gSynaptic pathology (loss of synaptic structure) scored as in source references and references [12,18,20].

^hRetinal pathology is scored by cumulative Aβ40 peptide or Aβ42 peptide load as described in Table 2 (right-most column).