The aim of the present study was to better characterize the cognitive phenotype in a large cohort children with 22q11DS compared with sibling controls and to investigate if the cognitive deficits in 22q11DS were modulated by COMT expression.
Aspects of FXTAS that are modeled well include elevated levels of Fmr1 mRNA, reduced levels of Fmrp, the presence of intranuclear inclusions that develop with age and show similar distributions within neurons, and neuropsychological and cognitive deficits, including poor motor function, impaired memory and evidence of increased anxiety.
Also, we replicated previous reports of GBA coding variants (rs2230288: p.E365K; rs75548401: rs75548401" genes_norm="2629">p.T408M) being associated with greater motor and cognitive decline over time, and an APOE E4 tagging variant (rs429358) being associated with greater cognitive deficits in patients.
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).
The APOE epsilon4 allele was associated with increased risk for cognitive deficits, whereas the MBL2 O/O genotype was associated with increased risk for progressive cognitive decline in Chinese individuals infected with HIV through contaminated blood products.
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.
Taken together, our data demonstrated that the reversal effect of FFPM on cognitive deficits in APP/PS1 transgenic mice might be related to stimulation of the cAMP/PKA/CREB/BDNF pathway and anti-inflammatory effects.
While the high activity alleles of variants within COMT have been associated with cognitive deficits, and the low activity alleles with higher risk of anxiety disorders, no associations of COMT with PEs have been found.
These results confirm that the presence of a family history of AD confers a subtle cognitive deficit in episodic memory as reflected by decreased drift rate that cannot be attributed to APOE.
Because mounting evidence suggests that epileptiform activity may play an important role in the development of AD-related cognitive deficits, we examined whether enhanced cleavage of Navβ2 occurs in APP transgenic mice, and whether it is associated with aberrant neuronal activity and cognitive deficits.
The epsilon 4 allele of apolipoprotein E (apoE4) is the predominant genetic risk factor for late-onset Alzheimer's disease (AD) and is also implicated in cognitive deficits associated with normal aging.
Surprisingly, humanized APP knock-in mouse models carrying a single APP Swedish mutation (AppNL), failed to develop amyloid plaque aggregation or cognitive deficits.