While Alzheimer's disease (AD) is traditionally associated with deficits in episodic memory, early changes in other cognitive domains, such as attention, have been gaining interest. In line with clinical observations, some animal models of AD have been shown to develop attentional deficits, but this is not consistent across all models. The APPswe/PS1ΔE9 (APP/PS1) mouse is one of the most commonly used AD models and attention has not yet been scrutinised in this model. We set out to assess attention using the 5-choice serial reaction time task (5CSRTT) early in the progression of cognitive symptoms in APP/PS1 mice, using clinically translatable touchscreen chambers. APP/PS1 mice showed no attentional changes across 5CSRTT training or any probes from 9 to 11 months of age. Interestingly, APP/PS1 mice showed increased impulsive and compulsive responding when task difficulty was high. This suggests that while the APP/PS1 mouse model may not be a good model of attentional changes in AD, it may be useful to study the early changes in impulsive and compulsive behaviour that have been identified in patient studies. As these changes have not previously been reported without attentional deficits in the clinic, the APP/PS1 mouse model may provide a unique opportunity to study these specific behavioural changes seen in AD, including their mechanistic underpinnings and therapeutic implications.
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http://dx.doi.org/10.1111/gbb.12594 | DOI Listing |
Mol Neurodegener
January 2025
Center for Cognition and Sociality, Life Science Institute (LSI), Institute for Basic Science (IBS), Daejeon, Republic of Korea.
Background: Alzheimer's Disease (AD) is a neurodegenerative disease with drastically altered astrocytic metabolism. Astrocytic GABA and HO are associated with memory impairment in AD and synthesized through the Monoamine Oxidase B (MAOB)-mediated multi-step degradation of putrescine. However, the enzymes downstream to MAOB in this pathway remain unidentified.
View Article and Find Full Text PDFJ Alzheimers Dis
January 2025
Key Laboratory of Basic Pharmacology of Guizhou Province, School of Pharmacy, Zunyi Medical University, Zunyi, China.
Background: One of the hallmark pathological characteristics of Alzheimer's disease (AD) is amyloid-β (Aβ) accumulated in brain, which is mainly derived from the proteolytic processing of amyloid-β protein precursor (AβPP). The ubiquitin-proteasome system is able to reduce Aβ generation by ubiquitination and degradation of AβPP. Icariin (ICA), a flavonoid isolated from Maxim.
View Article and Find Full Text PDFSci Transl Med
January 2025
Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder. Antiamyloid antibody treatments modestly slow disease progression in mild dementia due to AD. Emerging evidence shows that homeostatic dysregulation of the brain immune system, especially that orchestrated by microglia, plays an important role in disease onset and progression.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
January 2025
State Key Laboratory of Ophthalmology, Optometry, and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, China.
Purpose: Changes associated with Alzheimer's disease (AD) may have measurable effects on the retina, which may facilitate early detection due to the eye's accessibility. Retinal pathology and the regulation of serine racemase (SR) were investigated in the retinas of APP(SW)/PS1(∆E9) mice.
Methods: SR in the retinas and the content of D-serine in the aqueous humor were analyzed.
Foods
January 2025
School of Public Health, Health Science Center, Ningbo University, Ningbo 315211, China.
Alzheimer's disease (AD) is marked by impaired cognitive functions, particularly in learning and memory, owing to complex and diverse mechanisms. Methionine restriction (MR) has been found to exert a mitigating effect on brain oxidative stress to improve AD. However, the bidirectional crosstalk between the gut and brain through which MR enhances learning and memory in AD, as well as the effects of fecal microbiota transplantation (FMT) from MR mice on AD mice, remains underexplored.
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