Table 1.

Pathological effects of presenilin FAD mutations observed in transgenic mice

Effect	References
Age-related neuronal loss	Chui et al. (1999); Sadowski et al. (2004))
Age-related synapse loss	Priller et al. (2007)
Increased synaptic sprouting in dentate gyrus following  entorhinal cortex lesioning	Kadish et al. (2002)
Increased dendritic spine densities on CA1 pyramidal neurons  at 4–5 months, densities becoming normal at 8–10 months	Auffret et al. (2009)
Age-related vascular pathology especially prominent in the  microvasculature with thinned and irregular vessels;  appearance of abnormally looped vessels as well as string  vessels	Gama Sosa et al. (2009)
Age-related Congo red- and thioflavin S-positive inclusions  and Alz50 labeling of hippocampal pyramidal neurons;  abnormally phosphorylated forms of tau by Western blotting;  insoluble 10 nm straight filaments that label with antiphosphotau  antibodies; PHF-positive neurons in ventral horn  of the spinal cord	Tanemura et al. (2006); Lazarov et al. (2007); Dewachter et al. (2008)
Reduced phosphorylation of serine 9 on glycogen synthase  kinase 3β (GSK-3β) in sciatic nerve, spinal cord and  hippocampus	Pigino et al. (2003); Tanemura et al. (2006)
Abnormally phosphorylated neurofilament proteins	Lazarov et al. (2007); Yang et al. (2009)
Slowed axonal transport associated with increased  phosphorylation of the kinesin light chain.	Pigino et al. (2003); Lazarov et al. (2007)
Increased lipid and protein peroxidation products in brain;  enhanced expression of components of the oxidative  phosphorylation pathway	Leutner et al. (2000); Eckert et al. (2001); LaFontaine et al. (2002); Mohmmad Abdul et al. (2004); Schuessel et al. (2006); Fu et al. (2009)
Increased aneuploidy in spleen cells	Boeras et al. (2008)
Increased cathepsin D levels by Western blotting and more  cathepsin D-immunoreactive neurons with aging	Cataldo et al. (2004)
Decreased acetylcholinesterase (AChE) activity and alteration  of AChE glycosylation	Silveyra et al. (2008)
Elevated levels of apolipoprotein E in the brain	Tamboli et al. (2008)
Increased expression and activity of BACE1	Giliberto et al. (2009)
Larger and more sustained induction of LTP in hippocampal  slices	Parent et al. (1999); Barrow et al. (2000); Zaman et al. (2000);  Dewachter et al. (2008); Auffret et al. (2009); Wang et al. (2009)
Decreased anxiety; altered novel object recognition;  augmented contextual fear conditioning; impaired motor  performance; Morris water maze-normal in most studies but  impaired in one study of >1 year old PS2 FAD mutant mice	Vaucher et al. (2002); Lalonde et al. (2003); Lazarov et al. (2007);  Dewachter et al. (2008); Yuk et al. (2009)
Increased sensitivity to kainate-induced excitotoxic  hippocampal injury	Guo et al. (1999); Grilli et al. (2000); Schneider et al. 2001)
Increased sensitivity to trimethyltin-induced hippocampal  damage	Kassed et al. (2003)
Excessive neuronal loss in the entorhinal cortex following  lesioning of the perforant path	Lazarov et al. (2006)
Impaired hippocampal neurogenesis in adult brain	Wen et al. (2002b); Wang et al. ( 2004); Wen et al. (2004);  Chevallier et al. (2005); Zhang et al. (2007); Choi et al. (2008)