In this study, we examined the effect of obovatol on cognitive deficits in two separate AD models: (i) mice that received intracerebroventricular (i.c.v.) infusion of Aβ(1-42) (2.0 μg/mouse) and (ii) Tg2576 mice-expressing mutant human amyloid precursor protein (K670N, M671L).
These results suggest that phenotypes for onset and rate of cognitive decline vary with PSEN1 and APP genes, suggesting a behavioral heterogeneity in ADAD.
An amyloid precursor protein (APP) A673T mutation was found to be protective against Alzheimer's disease (AD) and cognitive decline in the Icelandic population and to associate with decreased levels of plasma β-amyloid in a Finnish population-based cohort.
We previously found that a mutation in APP that prevents this caspase cleavage ameliorated synaptic loss and cognitive impairment in a murine AD model.
This study demonstrates that the Arctic APP mutation is sufficient to cause amyloid deposition and cognitive dysfunction, and thus the TgAPParc mouse model provides a valuable tool to study the effect of the Arctic mutation in vivo without possible confounding effect of other APP mutations.
Deposition of amyloid-β (Aβ), the proteolytic product of the amyloid precursor protein (APP), might cause neurodegeneration and cognitive decline in Alzheimer's disease (AD).
Furthermore, overexpression of wild-type BACE1, but not non-SUMOylated K501R mutant, facilitates senile plaque formation and aggravates the cognitive deficit seen in the APP/PS1 AD mouse model.
We found a coding mutation (A673T) in the APP gene that protects against Alzheimer's disease and cognitive decline in the elderly without Alzheimer's disease.
Disorders associated with early-life alterations in amyloid precursor protein production or processing are associated with a distinct pattern of early striatal fibrillary Aβ deposition before significant cognitive impairment.
3xTg mice, which express an APP/PS1 mutation combined with a tau (P301L) mutation and that develop cognitive deficits at 6 months of age, were subjected to ELF-MF (50Hz, 500μT) exposure or sham exposure daily for 3 months.
We found a novel APP mutation (A673V) in the homozygous state in a patient with early-onset AD-type dementia and in his younger sister showing initial signs of cognitive decline.
Surprisingly, humanized APP knock-in mouse models carrying a single APP Swedish mutation (AppNL), failed to develop amyloid plaque aggregation or cognitive deficits.
Therefore, we investigated the mechanisms of the effects of Cy3G on beta-amyloid 25-35 (Aβ25-35)-induced SH-SY5Y cell injury and cognitive impairment in the APP(swe)/PS1(ΔE9) (PAP) mouse model of AD.
Reversal of high fat diet-induced obesity improves glucose tolerance, inflammatory response, β-amyloid accumulation and cognitive decline in the APP/PSEN1 mouse model of Alzheimer's disease.
Our data also indicate that introduction of the Swedish mutation alone in endogenous APP is not sufficient to produce either AD-related brain pathology or cognitive deficits in mice.
Indeed, the most popular genetic AD mouse lines bearing mutations of the amyloid precursor protein (APP) and presenilin 1 genes (PS1), often fail to present robust cognitive deficits or show them only at very advanced ages.
In two unrelated UK families with APP 717 val-ile mutations there was early prominent memory impairment with dyscalculia proceeding to generalized cognitive impairment with a lack of insight.
Behavioral sensitivity of the circular platform task was then shown through its ability to discern cognitive impairment in 7-month-old transgenic mice, carrying the mutant APP(SW) gene for early-onset Alzheimer's disease in humans, from non-transgenic litter-mates.
This interpretation of one aspect of the cognitive deficit in human mutant APP mice has parallels to deficits observed in patients with Alzheimer's disease, further supporting the validity of transgenic models of the disease.