TABLE 1.

Models of Aberrant Developmentally Important Proteins Purported to Be of Relevance for Alzheimer’s Disease

Gene Product	Type of Model	Characterization
Presenilin-1	Humanized mutants, mice	Some combined with mutant APP; some have amyloid plaques, increased levels of Aβ, or both; many have no apparent cognitive impairment
Presenilin-2	Humanized mutants, mice	Increased levels of Aβ
APP	Mutant mice	Some combined with mutant Presenilin-1; amyloid plaque burden is variable
ApoE	Knock-out and targeted mutation, mice	Alterations in immune system regulation, nerve regeneration, and muscle differentiation
p75NTR	Spontaneous mutants (negative) in PC12 cells; siRNA and shRNA downregulated in PC12 cells; exon III–deleted mice; exon IV–deleted (p75NTR knock-out) mice	PC12 cells abnormally susceptible to oxidant stress; exon III–deleted mice with subtle, variable changes in peripheral nerve regenerative capacity; exon IV–deleted mice with 28% increase in number of cholinergic neurons
Reelin	Autosomal recessive mutation, mice	Severe ataxia; inverted cortical lamination; abnormal positioning of neurons; aberrant orientation of cell bodies and fibers; cerebellar hypoplasia
VLDLR	Knock-out mice	Continued migration of cortical neurons past normal stop point; clinical phenotype like Reelin mutants but milder, unless combined with ApoER2 mutation
ApoER2	Mutation, mice	Failure of migration of late-generated neocortical neurons; clinical phenotype like Reelin mutants but milder, unless combined with VLDLR mutation
Notch	Mice with null heterozygous mutations in Notch1	Deficits in spatial learning and memory

APP = amyloid precursor protein; ApoE = apolipoprotein E; p75NTR = p75 neurotrophic receptor; siRNA = small, interfering RNA; shRNA = short hairpin RNA; VLDLR = very-low-density lipoprotein receptor; ApoER2 = apolipoprotein E receptor 2.