M344 also increases levels of immature APP, supporting an effect on APP trafficking, concurrent with the observed increase in MINT2 and FE65, both shown to increase immature APP in the early secretory pathway.Chronic i.p. treatment of the triple transgenic (APP<sub>sw</sub>/PS1<sub>M146V</sub>/Tau<sub>P301L</sub>) mice with M344, at doses as low as 3 mg/kg, significantly prevented cognitive decline evaluated by Y-maze spontaneous alternation, novel object recognition, and Barnes maze spatial memory tests.
The high accumulation of the CB-RBCMs in neurons resulted in a decrease in the neurotoxicity of CB and an increase in the migratory activity of neurons, and alleviated cognitive decline in APP/PS1 transgenic (Tg) mice.
MT5-MMP emerges as a new pro-amyloidogenic regulator of APP metabolism, whose deficiency alleviates amyloid pathology, neuroinflammation and cognitive decline.
To further explore how MgT treatment inhibits cognitive decline in APP/PS1 Tg mice, the critical molecules for amyloid precursor protein (APP) cleavage and signaling pathways were investigated.
Exposure to As-, Cd-, and Pb-mixture induces Aβ, amyloidogenic APP processing and cognitive impairments via oxidative stress-dependent neuroinflammation in young rats.
In this study, we investigated the effect of T4 on cognitive decline and synaptic plasticity in five times familial AD (5XFAD) mice co-expressing mutated amyloid precursor protein and presenilin-1.
However, the most widely used transgenic AD models (overexpressing mutated forms of amyloid precursor protein, presenilin, and/or tau) do not demonstrate the degree of inflammation, neurodegeneration (particularly of the cholinergic system), and cognitive decline that is comparable with the human disease.
The studied dendrimers did not reverse memory impairment in APP/PS1 mice following chronic administration; moreover, cationic G4mOS caused cognitive decline in nontransgenic mice.
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.
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.
The results suggest interaction between chronic cerebral hypoperfusion and APP(Sw/Ind) overexpression in cognitive decline in mice through enhanced neuronal loss and altered amyloid β metabolism.
These results offer additional support for the negative impact of apoE4 on both memory and attention and further suggest that APP-Yac/apoE-TR mice provide a novel and useful model for investigating the role of apoE in mediating susceptibility to cognitive decline.
The findings unveil a previously unrecognized role of Nox2-derived radicals in the behavioral deficits of Tg2576 mice and provide a link between the neurovascular dysfunction and cognitive decline associated with amyloid pathology.
Thus, changes in APP and tau expression may cause perturbed axonal transport and changes in APP processing, contributing to cognitive decline and neurodegeneration in Alzheimer's disease.
Interleukin-6 (IL-6), an inflammatory cytokine, is thought to play a role in neurodegeneration of the central nervous system and has been associated with increased amyloid precursor protein expression in vitro and greater cognitive decline.
Since interleukin-1 (IL-1) is an APP gene promoter showing a progressive increase in body fluids in parallel with mental deterioration in AD patients, we have studied the effects of CDP-choline on cognition, several biological parameters, and IL-1 beta production in AD and multi-infarct dementia (MID) in order to elucidate whether this compound alone or in combination with other drugs is able to restore immune function and improve mental performance in senile dementia.
Analysis of cognitive performance and polymorphisms of SORL1, PVRL2, CR1, TOMM40, APOE, PICALM, GWAS_14q, CLU, and BIN1 in patients with mild cognitive impairment and cognitively healthy controls.
We examined the effect of the novel Alzheimer's disease (AD) risk variant rs11136000 single nucleotide polymorphism in the clusterin gene (CLU) on longitudinal changes in resting state regional cerebral blood flow (rCBF) during normal aging and investigated its influence on cognitive decline in presymptomatic stages of disease progression.
In the present study CLU genotypes and haplotypes were associated with baseline cognition and the rate of cognitive decline in two cohorts, the Danish 1905 birth cohort (93 years of age in 1998) and the Longitudinal Study of Aging Danish twins (LSADT) (73-83 year old twins in 1997).