Skip to main content
. Author manuscript; available in PMC: 2011 Jun 10.
Published in final edited form as: Neuron. 2010 Jun 10;66(5):631–645. doi: 10.1016/j.neuron.2010.04.031

TABLE 1. Comparison of memory loss in aging rodents and APP rodents.

Shaded boxes indicate studies that directly compared phenotypes of transgenic mice and age-matched and older non-transgenic mice of the same background strain.

Similarities Aged rats & mice Citations Transgenic APP mice and Aβ-
infused rats
Citations
Neurological
deficits
Neophobia in aged FVB/N mice Hsiao et al. (1995) Neuron.
15(5):1203–18.
Neophobia in FVB/N mice with APP
transgenes
Hsiao et al. (1995) Neuron.
15(5):1203–18.
Hypometabolism
in specific brain
regions
Hypometabolism in brain regions
linked to memory function in aged
FVB/N mice
Hsiao et al. (1995) Neuron.
15(5):1203–18.
Hypometabolism in brain regions
linked to memory function in FVB/N
mice with APP transgenes
Hsiao et al. (1995) Neuron.
15(5):1203–18.
Deficits in LTP
likely due to
increased GABA
inhibition
Significantly greater enhancement of
LTP by bicuculline in aged mice than
in young adult mice
Yoshiike et. al (2008) PLoS One.
3(8): e3029.
Significantly greater enhancement of
LTP by bicuculline in young adult
APP/PS1 transgenic mice than in
young adult non-transgenic mice
Yoshiike et. al (2008) PLoS One.
3(8): e3029.
In vivo LTP
maintenance
impaired
Impaired maintenance, but not
induction, of hippocampal LTP in
aged rats
Barnes et al. (1979) J Comp
Physiol Psychol. 93(1): 74–104.
Impaired maintenance, but not
induction, of hippocampal LTP in
transgenic mice (Tg2576, APP/PS1)
and in Aβ-infused rats
Chapman, et al. (1999) Nat
Neurosci 2(3): 271–6
Gureviciene et al. (2004)
Neurobiol Dis. 15(2): 188–95.
Walsh et al. (2002) Nature
416(6880): 535–9.
Hippocampal
hyperexcitability
Increased firing rates of CA3 place
cells in aged rats
Wilson et al. (2005) J
Neurosci. 25(29):6877–86.
Spontaneous seizure activity in
hippocampal networks
Palop et al. (2007) Neuron.
55(5):697–711.
Impaired Ca2+
homeostasis in
neurons
Ca2+ elevated in neurons of aged rats;
Ca2+ elevated in pre-synaptic
terminals of aged rats; altered
sources of Ca2+ influx during induction
of LTP in aged rats; Ca2+ chelation
restores LTP in slices from aged rats
but reduces LTP in slices from young
rats and reverses memory deficits in
aged rats;
Hajieva et al. (2009) Neurosci
Lett. 451(2): 119–23.
Tonkikh et al. (2006) Exp Neurol.
197(2): 291–300.
Shankar et al. (1998) J
Neurophysiol. 79(1): 334–41.
Boric et al. (2008) J Neurosci.
28(32): 8034–9.
Reviewed in Foster TC (2007)
Aging Cell. 6(3): 319–25.
No studies yet reported in pre-plaque
APP transgenic mice that do not also
contain a mutant PS1 transgene,
which itself disrupts Ca2+ dynamics
Reviewed in Green & LaFerla (2008) Neuron. 59(2): 190–4.
Stutzman GE (2007)
Neuroscientist. 13(5): 546–59.
Hypothalamic-
pituitary-adrenal
(HPA) stress
response defect
Impaired HPA response to restraint-
induced stress
Bizon et al. (2001) Eur J
Neurosci. 14(10): 1739–51
Aberrant HPA stress response to
hypoglycemia in Tg2576 mice
Pedersen et al. (1999) J Mol
Neurosci. 13:(1–2): 159–65.
Preservation of
neuron number in
hippocampus
No neuronal loss in hippocampus of
aged rats with spatial memory deficits
Rapp & Gallagher (1996) Proc
Natl Acad Sci U S A. 93(18): 9926–
30.
No neuronal loss in hippocampus of
memory-impaired Tg2576 mice or in
aged PDAPP mice
Irizarry et al. (1997) J
Neuropathol Exp Neurol. 56(9):
965–73.
Irizarry et al. (1997) J Neurosci.
17(18): 7053–9.
Cholinergic
system changes
Shrinkage of basal forebrain neurons Reviewed in Finch CE (1993)
Trends Neurosci. 16(3): 104–10.
Cholinergic terminal reorganization in
Tg2576 × PS1 mice; basal forebrain
neuron shrinkage in TgAPP mice with
London mutation
Wong et al. (1999) J Neurosci.
19(7): 2706–16.
Bronfman et al. (2000) Neurobiol
Dis. 7(3): 152–68.
Oxidative stress
markers
increased
Increased signatures of oxidative
stress in aged rats with spatial
memory deficits
Nicolle et al. (2001)
Neuroscience. 107(3): 415–31.
Increased oxidative stress markers in
aged Tg2576 mice
Smith et al. (1998) J Neurochem.
70(5): 2212–5.
Pappolla et al. (1999) J Pineal
Res. 27(4): 226–9.
Pratico et al. (2001) J Neurosci.
21(12): 4183–7
Caloric
deprivation
Caloric deprivation prevents memory
loss in rats
Pitsikas & Algeri (1992)
Neurobiol Aging. 13(3): 369–73.
Caloric restriction decreases amyloid
deposition in APP and APP/PS1
mice; preserves spatial memory in
Tg2576 mice
Patel et al. (2005) Neurobiol
Aging. 26(7): 995–1000.
Mouton et al. (2009) Neurosci
Lett. 464(3): 184–7.
Qin et al. (2008) Ann N Y Acad
Sci. 1147: 335–47.
Beneficial effects
of COX inhibition
Nimesulide (COX-2 inhibitor)
attenuates memory deficits in aged
mice; NSAIDs (nimesulide, rofecoxib,
naproxen) reverse memory deficits in
aged mice, no effect in young mice
Bishnoi et al. (2005)
Methods Find Exp Clin Pharmacol.
27(7): 465–70.
Jain et al. (2002) Behav Brain
Res. 133(2): 369–76.
NSAIDs prevent (ibuprofen) or
reverse (ibuprofen, naproxen, MF-
tricyclic) memory deficits in Tg2576
mice, no effect in non-tg
Kotilinek et al. (2008) Brain.
131(Pt 3): 651–64.
PKC-gamma
elevation
Increased in aged rats with spatial
memory deficits
Colombo et al. (1997) Proc Natl
Acad Sci U S A. 94(25): 14195–9.
Colombo & Gallagher (2002)
Hippocampus. 12(2): 285–9.
Increased in aged Tg2576 mice Rossner et al. (2001) Eur J
Neurosci. 13(2): 269–78.
Environmental
enrichment
Environmental enrichment improves
memory performance in aged but not
young male mice; exercise improves
memory in younger female mice, but
exercise + cognitive enrichment
needed to improve memory in older
female mice
Harburger et al. (2007) Behav
Brain Res. 185(1): 43–8.
Harburger et al. (2007) Behav
Neurosci. 121(4): 679–88.
Exercise, social interactions and
cognitive enrichment improve
cognitive function in APP and
APP/PS1 transgenic mice, but also
improve cognitive function in non-
transgenic
controls
Costa et al. (2007) Neurobiol
Aging 28: 831–844.
Jankowsky et al. (2005) J
Neurosci. 25(21):5217–5224.
Brain Aβ
elevation
Murine Aβ rises with age in mice Fukumoto et al. (2004) Am J
Pathol. 164(2): 719–25.
Human Aβ rises with age in APP
transgenic mice
Games et al. (1995) Nature.
373(6514): 523–7.
Hsiao et al. (1996) Science.
274(5284): 99–102.
Sturchler-Pierrat et al. (1997)
Proc Natl Acad Sci U S A.
94(24): 13287–92.
Chishti et al. (2001) J Biol Chem.
276(24): 21562–21570.
Differences Aged rats & mice Citations Transgenic APP mice and Aβ-
infused rats
Citations
Amyloid deposits None (rodent Aβ) Present (human Aβ)
AMPA binding in
hippocampus
No change in aged rats; no
relationship to memory
Nicolle et al. (1996)
Neuroscience. 74(3): 741–56.
Increased in aged Tg2576 mice Cha et al. (2001) Neurobiol Dis.
8(1): 90–102.
NMDA binding in
hippocampus
Decreased in aged rats; inverse
relationship to memory
Nicolle et al. (1996)
Neuroscience. 74(3): 741–56.
Adams et al. (2001) J Comp
Neurol. 432(2): 230–43.
No change in aged Tg2576 mice Cha et al. (2001) Neurobiol Dis.
8(1): 90–102.
Effect of SOD2
overexpression
SOD2 over expression has no effect
on age-associated memory
impairment or LTP
Hu et al. (2007) Neurobiol Learn
Mem. 87(3): 372–84.
SOD2 over expression prevents
memory impairments in Tg19959
mice
Dumont et al. (2009) FASEB J.
23(8): 2459–66.