1. Probing the Biology of Alzheimer's Disease in Mice
Karen H. Ashe, Kathleen R. Zahs 
Neuron 
Volume 66, Issue 5, Pages (June 2010)
DOI: /j.neuron
Copyright © 2010 Elsevier Inc. Terms and Conditions

2. Figure 1 APP and Its Major Proteolytic Products
Cleavage of APP by α-, β-, γ-, and ɛ-secretases produces secreted amino-terminal fragments, carboxyl-terminal polypeptides, and Aβ. (Ma et al., 2007; copyright 2007, National Academy of Sciences, USA.)
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3. Figure 2
Regional Hypometabolism in APP Transgenic Mice and People at Risk for AD
MRI and [18F]-FDG-PET scans of (A) a control subject and (B) a carrier of a presenilin-1 mutation associated with familial autosomal-dominant AD, 27 years before mean age of onset of dementia in her family. Bilateral hypometabolism of parietal cortex and medial temporal lobe is evident on PET in the absence of atrophy on MRI. (C) Regional cerebral glucose utilization, monitored with [14C]2-deoxyglucose, in the cortex and hippocampus of a neophobic transgenic FVB/N mouse expressing human APP with a disease-linked mutation. Compared to its nontransgenic littermate, the transgenic mouse shows decreases in glucose utilization in cerebral cortex and hippocampus. Pseudocolored images of autoradiograms of coronal sections through cerebral cortex, hippocampus, and anterior brainstem; warmer colors represent greater glucose uptake. (D) Magnified view of (C) showing hippocampus and overlying cerebral cortex. (A and B) Reprinted by permission of the Society of Nuclear Medicine from Mosconi et al. (2006). (C and D) Reprinted with permission from Elsevier from Hsiao et al. (1995).
Neuron  , DOI: ( /j.neuron )
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4. Figure 3 APP Transgenic Mice Model Asymptomatic Alzheimer's Disease
APP transgenic mice exhibit functional abnormalities similar to those observed in people at risk for Alzheimer's disease but do not display the loss of neurons seen in people clinically diagnosed with mild cognitive impairment or Alzheimer's disease.
Neuron  , DOI: ( /j.neuron )
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5. Figure 4
Ab Initiates a Disease Process that Might Progress to a Stage of Cognitive Impairment, but Tau Mediates Cognitive Dysfunction
In this hypothetical scheme, Aβ∗56 (see “Soluble Aβ Oligomers Are Associated with Memory Deficits in APP Transgenic Mice”) and perhaps other Aβ oligomers cause synaptic dysfunction that manifests as subtle cognitive deficits in APP transgenic mice and in people in the asymptomatic phase of AD. Toxic Aβ oligomers surrounding plaques locally damage neurons, but their effects on cognition are unknown (see “Plaque-Associated Abnormalities”). Abnormal tau processing triggered by pathological forms of Aβ in AD, and by mutations in tau transgenic mice, causes loss of synapses and neurons and cognitive deficits severe enough to warrant a diagnosis of mild cognitive impairment (MCI) or AD. The effects of NFTs, rather than soluble pathological forms of tau, are unknown (see “Targets of Aβ”). It is also not known whether the same effector molecules/mechanisms responsible for Aβ-induced synaptic and cognitive dysfunction trigger tau abnormalities or whether a separate pathway is involved.
Neuron  , DOI: ( /j.neuron )
Copyright © 2010 Elsevier Inc. Terms and Conditions