Changes in the brain and plasma Aβ peptide levels with age and its relationship with cognitive impairment in the APPswe/PS1dE9 mouse model of Alzheimer’s disease

The role of neuroinflammation and amyloid in cognitive impairment in an APP/PS1 transgenic mouse model of Alzheimer's disease

“…To analyze amyloid pathology in this transgenic mouse model, we have utilized three different Aβ staining methods. We found amyloid plaques as young as at 3 months of age, which is agreement with previous reports . The majority of plaques were small and compact at 5 months old in transgenic mice, and the morphology of plaques gradually became bigger and more diffuse as animals aged.…”

“…22,23 Interestingly, however, earlier animal studies have shown an age-dependent spatial memory deterioration in APP/ PS1 mice using the Morris water maze or T maze. 20,24 This observed discrepancy among different animal models might be due to differences in mouse genetic backgrounds and transgenes, which also reveals some of the challenges in finding a perfect animal model of AD.…”

“…APP/PS1 mice have been reported to exhibit an age-dependent deterioration in the overall performance in a water maze test. 20 Thus, we averaged escape latencies to reach the hidden platform of APP/ PS1 mice in all trials of each day during acquisition and compared them to their age-matched WT mice which were defined as 100%, the differences in the overall performance between APP/PS1 and their counterparts indeed progressively increased up to the age of 9 months but then plateaued at the age of 12 months (P<.0036, Figure 3), and the averaged latencies were larger in the transgenic mice (2.09% at 3 months P>.05, 13.91% at 5 months P=.0765, 22.93% at 9 months P<.05, 21.18% at 12 months P<.05, Figure 3).…”

Kalirin reduction rescues psychosis-associated behavioral deficits in APPswe/PSEN1dE9 transgenic mice

“…We therefore sought to evaluate this hypothesis by reducing kalirin protein levels in mice transgenic for humanized APP and PSEN1 ( APPswe/PSEN1dE9 ) , each containing causal mutations for AD (Jankowsky et al, 2004). The APPswe/PSEN1dE9 model demonstrates detectable Aβ deposits by 4 months of age, with increasing levels of soluble and insoluble Aβ up to at least 12 months of age (Izco et al, 2014; Jankowsky et al, 2004). The combined mutations produce Aβ 1–42 as the predominant Aβ species resulting in an increased ratio of Aβ 1–42 /Aβ 1–40 compared to mice transgenic for the APP swe mutation alone (Jankowsky et al, 2004).…”

Plasma amyloid beta peptides: an Alzheimer’s conundrum or a more accessible Alzheimer’s biomarker?

“…Recent studies of plasma Aβ levels have shown that they recapitulate the same sink-model trends observed in CSF (albeit with considerably lower Aβ levels in plasma): higher than normal Aβ1-42 levels at preclinical stages, which drop longitudinally with disease onset and progression. This paradigm is supported by the following observations: (i) higher levels in early onset, genetically associated AD, such as in Down's syndrome and autosomal dominant AD (ADAD), and even as early as children with ADAD [11]; (ii) higher levels in animal models prior to disease onset [17]; (iii) associations with cognitive change in normal individuals [14]; and (iv) association between plasma and CSF levels [18], in longitudinal studies being predictive of progression to AD [19]. For plasma Aβ, some empirical questions that still need to be resolved are as follows: (i) How much is derived from the CNS versus peripheral sources?…”